Ma `lumot

Saraton hujayralarining shikastlanishi


Men saratonning molekulyar biologiyasi haqida o'qidim, boshimda tartibsizlik va ko'plab savollar bor ...

Mening asosiy savolim-

Saraton hujayralarining shikastlanishi dna ketma -ketligida yoki gen ifodasida (mikroRNK) bormi? yoki hatto boshqa narsa?

Rahmat :)


Saraton, odatda, genom mutatsiyalari natijasida kelib chiqadigan, tinimsiz uyali replikatsiya deb ta'riflanadi.

Saratonni keltirib chiqaradigan mutatsiyalar aniqlangan genlar deb nomlanadi onkogenlar; COSMIC (Saraton kasalligining somatik mutatsiyalari katalogi) ma'lumotlar bazasida barcha ma'lum onkogenlar ro'yxati keltirilgan (547 yildan 2015 yil 23 yanvargacha - barcha inson genlarining 1 foizi!) [1].

The ta'siri ma'lum bir mutatsiyaning gen yoki gen ifodasini qandaydir tarzda o'zgartirishi mumkin. Bu to'g'ridan-to'g'ri, masalan, o'simtani bostiruvchi genni o'z vazifasini bajara olmasligini ko'rsatishi mumkin [2] yoki bilvosita, masalan, epigenetik mexanizmlarga ta'sir qilish, bu o'z navbatida hujayra tsiklini tartibga solishda ishtirok etuvchi genlar ekspresiyasiga ta'sir qiladi [3].

Men bilganimdek, saraton faqat genning ifodalanishidagi o'zgarish tufayli yuzaga kelmaydi, garchi u vositachilik qilsa. Hujayraning nazoratsiz bo'linishiga olib keladigan gen ekspresiyasi yoki samaradorligining o'zgarishi (masalan, p53 o'simtani bostiruvchi) sabab bo'ldi genomik darajadagi mutatsiyalar orqali.

Mutatsiyaga nima sabab bo'ladi?

Ko'p omillar mutatsiyaga olib kelishi mumkin, kimyoviy moddalardan (masalan, sigaret tutunidan, nafaqat o'pkada [4]), DNKning replikatsiya mexanizmidagi xatolarga qadar, chunki somatik hujayralar normal hujayralar bo'linishidan o'tadi [5].

U erda oxirgi ma'lumotnoma ba'zi to'qimalarning boshqalarga qaraganda saraton kasalligiga ko'proq moyil bo'lishini isbotlovchi dalillarni beradi; hujayralar almashinuvi yuqori bo'lgan (va shuning uchun hujayralar bo'linishini talab qiladigan) to'qimalarda saraton kasalligi yuqori bo'ladi - quyidagi rasmga qarang [5]! Bu raqam "o'pka saratoni" ni ikki guruhga ajratadi, bu shuni ko'rsatadiki, chekmaydiganlar ham o'pka saratoni rivojlanish xavfiga ega, lekin sigaret chekadiganlarnikidek xavfi yuqori emas.


  1. http://cancer.sanger.ac.uk/cancergenome/projects/census/
  2. Myuller, P.A.J .; Vousden, K.H. (2013) saraton kasalligida p53 mutatsiyalari. Nat Cell Biol. 15:2-8
  3. Hamamoto, R .; Saloura, V .; Nakamura, Y. (2015) Odam o'smasida giston bo'lmagan oqsil lizin metilatsiyasining muhim rollari. Nat Rev Saraton kasalligi. 15:110-124
  4. Buyuk Britaniyaning saraton tadqiqotlari chekish va saraton haqida hisobot
  5. Tomasetti, C. va Vogelshteyn, B. (2015) To'qimalar orasidagi saraton xavfining o'zgarishini ildiz hujayralarining bo'linishi bilan izohlash mumkin. Ilm 347, 78-81

Radiatsiyaning saraton hujayralariga biologik ta'siri

Radioterapevtik onkologiya, kompyuter texnologiyalari va tibbiy tasvirlash texnologiyalari rivojlanishi bilan nurli terapiya katta yutuqlarga erishdi. Radiatsiyaning o'smalarga ta'siri va o'ziga xos mexanizmini o'rganish saraton kasalligini davolashda markaziy mavzuga aylandi. An'anaviy fikrga ko'ra, nurlanish DNKning ikki spirali tuzilishiga bevosita ta'sir qilishi mumkin, bu esa o'z navbatida apoptoz, nekroz va qarishni qo'zg'atish uchun DNKning shikastlanish sezgichlarini ishga soladi yoki mitozning normal hodisalariga ta'sir qiladi va oxir -oqibat neoplazma hujayralarining turli biologik xususiyatlarini qaytaradi. Bundan tashqari, nurlanish hujayra osti tuzilmalariga zarar etkazadi, masalan, sitoplazmatik membrana, endoplazmatik retikulum, ribosoma, mitoxondriya va saraton hujayralarining lizosomasi, o'simta hujayralarining turli biologik faolligini tartibga soladi. So'nggi tadqiqotlar shuni ko'rsatdiki, nurlanish o'simta hujayralari fenotipini, immunogenligini va mikro muhitini ham o'zgartirishi mumkin va shu bilan butun dunyo bo'ylab saraton hujayralarining biologik xatti -harakatlarini o'zgartiradi. Ushbu sharhda biz kombinatsion terapiya uchun nazariy asos yaratish va onkologiyada yangi davrni ochish uchun o'simta hujayralarining biologik xususiyatlariga terapevtik nurlanish ta'siriga e'tibor qaratamiz.


Genomik beqarorlik va saraton: kirish

Genomik beqarorlik - bu hujayralarning hayotiy tsikli davomida genomning o'zgarishi tendentsiyasining oshishi. Bu shish paydo bo'lishining asosiy harakatlantiruvchi kuchi. Hujayra bo'linishi paytida genomik beqarorlik to'rtta asosiy mexanizm yordamida minimallashtiriladi: S fazada DNKning yuqori aniqlikdagi replikatsiyasi, mitozda xromosomalarning aniq segregatsiyasi, DNKning sporadik shikastlanishini xatosiz tuzatish va hujayra tsiklining muvofiqlashtirilgan rivojlanishi. Ushbu kirish genomik beqarorlik va o'simgenezning oldini olish sharoitida ushbu mexanizmlarga yordam beradigan asosiy molekulyar jarayonlarni umumlashtiradi.

Genomik beqarorlik o'simtogenezning asosiy harakatlantiruvchi kuchi sifatida

Ko'pchilik saraton bo'lmagan somatik hujayralar uchun hujayra bo'linishining asosiy maqsadi genomni to'g'ri takrorlash va keyin takrorlangan genomni ikkita qiz hujayraga teng ravishda taqsimlashdir. Bu qiz hujayralar ota -ona hujayrasi bilan bir xil genetik materialga ega bo'lishini ta'minlaydi. Bu maqsadga erisha olmaslik yoki bu jarayonda g'ayritabiiy ravishda yuqori chastotali xatolar qiz hujayralarda turli xil genom o'zgarishlariga olib keladi. Bu o'zgarishlarga ma'lum genlardagi mutatsiyalarning har xil shakllari, kuchayishi, xromosoma segmentlarining o'chirilishi yoki qayta joylashishi, butun xromosoma (lar) ning ko'payishi yoki yo'qolishi va boshqalar kiradi. hujayra bo'linishi, hujayra o'sishi va o'limi o'rtasidagi nomutanosiblik va saraton. Genomik beqarorlik - bu genomik o'zgarishlarga moyil bo'lgan jarayon yoki genomik o'zgarishlarga moyillik kuchayishi. Hujayralarning bo'linishi paytida genomik beqarorlik ota -ona hujayralarining genomni aniq takrorlay olmasligi va genomik materialni qiz hujayralar o'rtasida aniq taqsimlay olmasligi bilan bog'liq.

Oddiy to'qimalarda hujayralar bo'linishi neoplastik transformatsiya yoki shish paydo bo'lishining oldini olish uchun qattiq tartibga solinadi. Shakl 1da soddalashtirilganidek, o'simta hosil bo'lishining molekulyar jarayonini bir qator hujayralar bo'linishi paytida genomik o'zgarishlarning to'planishi sifatida ko'rish mumkin. Ajdod hujayrasidagi tanqidiy genlarning o'zgarishi oddiy hujayrani saratongacha bo'lgan hujayraga aylantirishi mumkin. Garchi saratongacha bo'lgan hujayralar klinik jihatdan saraton kasalligi deb hisoblanmasa ham, qo'shimcha genomik o'zgarishlar ularning ba'zilariga o'sishining afzalliklariga ega bo'lish imkonini beradi. Shunday qilib, neoplastik hujayralarning yangi populyatsiyasi saraton tashxisi qo'yiladigan klinik holatga o'tishi mumkin. Saraton hujayralari orasidagi qo'shimcha genetik o'zgarishlar, yanada tajovuzkor xususiyatlarga ega bo'lgan hujayralarning kichik populyatsiyasiga olib kelishi mumkin. Shunday qilib, genomik o'zgarishlarning to'planishi nafaqat o'ziga xos belgi, balki o'sma paydo bo'lishining harakatlantiruvchi kuchi hamdir. Bu modeldagi muhim nuqta shundaki, neoplastik transformatsiya va progressiya davomida hujayra populyatsiyasining alohida kichik guruhlarida turli xil genetik o'zgarishlarning shakllari paydo bo'lishi va to'planishi mumkin. Bu saraton hujayralarida turli xil genetik ma'lumotlarga ega bo'lib, saraton kasalligida kuzatiladigan heterojenlikka yordam beradi.

Saraton genomik beqarorlik kasalligi sifatida va uning saraton kasalligiga aralashuvi.

Saraton genomik beqarorlik kasalligi sifatida va uning saraton kasalligiga aralashuvi.

Genomik yaxlitlikni saqlashning asosiy mexanizmlari

Saraton hujayraning nazoratsiz o'sishi natijasidir va hujayra bo'linishida genomik o'zgarishlarning to'planishi o'simtogenezning harakatlantiruvchi kuchi bo'lib, hujayralarning bo'linishi paytida genomik barqarorlik qanday saqlanishini tushunish to'qimalarning normal o'sishi paytida o'simtogenezning oldini olish mexanizmlarini ochib berish uchun juda muhimdir. . Asosan, oddiy sutemizuvchi hujayralar asosan hujayra bo'linishida genomik barqarorlikni saqlash uchun to'rtta mexanizmga murojaat qilishadi (2-rasmda ko'rsatilgan): (i) S-fazada DNK replikatsiyasining yuqori aniqligi, (ii) xromosomalarning to'g'ri taqsimlanishi. mitoz paytida qiz hujayralar, (iii) hujayra tsikli davomida DNKning shikastlanishini xatosiz tuzatish va (iv) hujayra tsiklining rivojlanishi va nazorat nuqtasini nazorat qilish. Hujayra taqdirini boshqarishning dis-regulyatsiyasi, shu jumladan apoptoz va qarilikni boshqa mexanizm (lar) genomik beqarorlikning oqibatlari sifatida qaralishi mumkin va bundan tashqari, saraton hujayralarining o'sish ustunligiga hissa qo'shishi mumkin. To'rtta asosiy mexanizmning har biri orasida bir nechta molekulyar jarayonlar ishtirok etadi.

Hujayra aylanishi davomida genomik barqarorlikni saqlashning asosiy mexanizmlarini ko'rib chiqish.

Hujayra aylanishi davomida genomik barqarorlikni saqlashning asosiy mexanizmlarini ko'rib chiqish.

DNK replikatsiyasining sodiqligi

S-fazada, butun genomik DNK aniq bir marta va har bir hujayra tsiklida takrorlanadi. Bu jarayonda xatolikka moyillik genomik beqarorlikni bildiradi. DNK replikatsiyasi bilan bog'liq genomik o'zgarishlarni minimallashtirishning asosiy mexanizmlari quyidagilardir. (i) DNK-polimerazalar yordamida tayanch-juftlik va tuzatish ishlarining yuqori aniqligi. (ii) Nafaqat mos keluvchi bazalarni, balki DNKning ikkilamchi tuzilmalarini, ayniqsa, takrorlanuvchi DNK ketma -ketligida, tuzatish uchun mos kelmaydigan ta'mirlash mashinalari. (iii) To'xtab qolgan replikatsiya vilkalarini o'z vaqtida hal qilish. DNKning replikatsiya vilkalari ko'pincha replikatsiya blokirovkasining turli shakllariga duch kelganidan keyin to'xtaydi yoki hatto qulab tushadi. Genomning to'liq takrorlanishini ta'minlash va genomning o'zgarishiga olib kelishi mumkin bo'lgan keyingi qulash ehtimolini minimallashtirish uchun bu to'xtab qolgan replikatsiya vilkalarini o'z vaqtida qayta ishga tushirish kerak. Bu jarayon gomologik rekombinatsiya va boshqa DNKni tiklash jarayonlarida ishtirok etadigan oqsillarni talab qiladi. (iv) Okazaki parchalarining pishishi. DNK sintezi vaqtida ortda qolgan ip ko'p Okazaki bo'laklari ko'rinishida takrorlanadi. Har bir Okazaki fragmentining 5-uchida RNK primeri va past DNK polimeraza sintez qilgan qisqa DNK segmenti (ya'ni a segmenti) mavjud. RNK primerlari va a segmentlari Okazaki bo'laklari bog'lanishidan oldin olib tashlanadi. Okazaki parchalanishining buzilishi genomik o'zgarishlarga olib kelishi mumkin. (v) Butun genomning hujayra tsikliga bir marta va faqat bir marta to'liq takrorlanishini ta'minlash uchun replikatsiya litsenziyalash mexanizmlari. Ushbu tartibga solish, ehtimol, S-fazadan oldin replikatsiya kelib chiqish joylarida oldindan replikatsiya kompleksini yig'ish orqali nazorat qilinadi. (vi) yangi sintez qilingan DNKdan xromosomalarning muvofiqlashtirilgan qayta yig'ilishi. (vii) Telomerlarni saqlash va yangi sintezlangan DNK va xromatin bo'yicha epigenetik imzolarni takrorlash kabi boshqa mexanizmlar ham replikatsiya ishonchliligi uchun muhim hisoblanadi.

Mitozda xromosomalarning aniq segregatsiyasi

S-fazada DNK va xromosomalar takrorlangandan so'ng, genomik beqarorlikka sezgir bo'lgan hujayra bo'linishining navbatdagi muhim bosqichi mitozdir. Mitoz paytida, singil xromatidlar qiz hujayralarda teng taqsimlanadi. Bu ko'plab jarayonlar bilan muvofiqlashtiriladi, jumladan: (i) xromosomalarning kondensatsiyasi, (ii) opa -xromatidlarning birlashishi, (iii) sentrosomaning ko'payishi va ajralishi, (iv) kinetoxorlarning yig'ilishi va biriktirilishi, (v) milning shakllanishi va nazorat nuqtasi, (vi) xromosomalarning ajratilishi. , (vii) sitokinez va boshqalar. Bu jarayonlarning har birining dis-regulyatsiyasi saraton kasalligida tez-tez uchraydigan xromatidlarning noto'g'ri segregatsiyasiga va aneuploidiya va poliploidiyaga olib keladi. Shuni alohida ta'kidlash kerakki, mitoz paytida ko'rsatiladigan genomik beqarorlik bilan bog'liq bo'lgan ba'zi xromosoma anormalliklari S fazali nuqsonlarning natijasi bo'lishi mumkin. Misol uchun, sentrosomalarning takrorlanishi DNK replikatsiyasi bilan muvofiqlashtirilgan deb ishoniladi va mitozga kirishdan oldin replikatsiya vositachilarining buzilgan rezolyutsiyasi mitotik xatolar xavfini oshiradi.

DNKning vaqti-vaqti bilan shikastlanishini xatosiz tuzatish

Hujayra tsikli davomida genom o'z -o'zidan va induktsiya qilingan DNK shikastlanishining turli shakllariga duch keladi. Agar bu shikastlanishlar tuzatilmasa, bu nafaqat hujayra funktsiyalariga ta'sir qiladi, balki DNK replikatsiyasi va xromosomalar segregatsiyasi paytida xatolar xavfini oshiradi. DNKning shikastlanishi bir nechta aniq belgilangan yo'llar bilan tuzatiladi, shu jumladan bazani olib tashlash, nukleotidlarni olib tashlashni tiklash, DNKning ikki qatorli uzilishini (DSB) tuzatish va boshqalar. DNKning kimyoviy shikastlanishi, asosan replikatsiya bilan bog'liq.

Genomik beqarorlikning ahamiyati shundaki, DNKni tiklash natijasi turlicha. DNKning ikkilamchi spiralining kimyoviy shikastlanishini bartaraf etish uchun ba'zi ta'mirlash jarayonlarining tugashi DNK ketma -ketligini o'zgartirishi yoki genom segmentlarini qayta tuzilishiga olib kelishi mumkin. Ushbu turdagi ta'mirlash "xatolarga moyil" deb nomlanadi. Shubhasiz, uning natijasi genomik beqarorlikka olib kelishi mumkin, garchi u DNKning dastlabki shikastlanishidan kelib chiqadigan boshqa genomik o'zgarishlarni oldini olsa. Bundan farqli o'laroq, boshqa ta'mirlash jarayonlari nafaqat DNKning kimyoviy shikastlanishini tuzatibgina qolmay, balki "xatosiz" ta'mirlash deb hisoblanadigan asl genom tuzilishini saqlab qolishi mumkin. Masalan, DNK DSBlarini ta'mirlash. DSBni gomologik rekombinatsiyalash genomik o'zgarishlarga olib kelishi ehtimoli kamroq, shuning uchun "xatosiz". Boshqa tomondan, homolog bo'lmagan birlashma yo'li mutatsiyalar va/yoki genomlarni qayta tuzish xavfiga ega, shuning uchun "xatolarga moyil". Biroq, bu tasnif xatolar ishlab chiqarishning nisbiy xavfiga asoslangan. Shuni yodda tutish kerakki, "xatolarga moyil" ta'mirlash har doim ham xato qilmaydi va "xatosiz" ta'mirlash ba'zida xatolarga olib keladi.

Ta'mirlash yo'llarining faoliyati va ularni boshqa hujayra funktsiyalari bilan muvofiqlashtirish (masalan, hujayra tsiklining rivojlanishi va hujayra o'limi) DNKning shikastlanish signalizatsiya tarmog'i bilan tartibga solinadi. Ushbu tarmoqning dis-regulyatsiyasi DNK shikastlanishini tuzatish bo'yicha kelishilgan sa'y-harakatlarni sezilarli darajada yomonlashtiradi, shuning uchun genomik beqarorlikka olib kelishi mumkin.

Genomik beqarorlik va o'simtogenezga ta'siridan tashqari, DNK shikastlanishini tuzatish yo'llari saraton kasalligini davolash uchun juda muhimdir. Radiatsiya va ko'plab kimyoterapevtik vositalar saraton hujayralarida DNK shikastlanishiga olib kelishi tufayli saraton kasalligini davolash uchun ishlatiladi. Shunday qilib, ta'mirlash qobiliyati terapevtik natijaning hal qiluvchi omilidir. Saraton hujayralarida DNKni to'g'ri tuzatish yo'lini maqsadli inhibe qilish terapevtik samaradorlikni oshirishning samarali usuli hisoblanadi.

Hujayra tsiklining rivojlanishini muvofiqlashtirish uchun nazorat punktlari

Hujayra bo'linishi tartibli tarzda olib borilganligi sababli, hujayra tsiklining rivojlanishi yuqori darajada muvofiqlashtirilgan. Hujayraning keyingi hujayra tsikli fazasiga erta kirishi genomik o'zgarishlarga moyillikni keltirib chiqaradi. Hujayra tsiklini nazorat qilish punktlari bir bosqichdan ikkinchisiga o'tish genomik o'zgarishlarning minimal xavfi ostida bo'lishini ta'minlash uchun qurilgan. Bu xavf omillari (G1/S/G2 fazasidagi DNKning shikastlanishi, anafazadan oldin milning anormalligi va boshqalar) yo'q qilinmaguncha keyingi bosqichga kirishni kechiktirish orqali amalga oshiriladi. Hujayra tsiklini nazorat qilish punktining yana bir muhim vazifasi - bo'linish havzasidan o'ta shikastlangan yoki xavfli hujayralarni yo'q qilish uchun ba'zi jarayonlarni (masalan, apoptoz, mitotik falokat va qarilik) samarali ishga tushirishdir.

Bir necha hujayrali tsiklli nazorat punktlarining mexanizmlari yaxshi yo'lga qo'yilgan. G1/S nazorat punkti shikastlangan hujayralarning S fazasiga kirishini cheklashdan iborat, chunki DNK shikastlangan hujayralarda DNK replikatsiyasi xatolarining xavfi yuqori bo'ladi. U hujayralarni G1/S chegarasida DNKning shikastlanishi va yuqori xavf omillari yo'qolguncha ushlab turadi yoki apoptoz va qarilikni qo'zg'atadi. G2/M nazorat punkti hujayralarning mitozga erta kirishiga to'sqinlik qiladi va shu tariqa xromosomalarni ajratish xatolarini kamaytiradi. In-S nazorat punkti replikatsiya xatolarini minimallashtirish uchun replikatsiyaning kelib chiqishini kechiktirishga yordam beradi yoki S fazasida DNKning takrorlanishini sekinlashtiradi. Mitotik milni nazorat qilish punkti xromosomalarni ajratish xatolarini minimallashtirish uchun milning normal ishlashini ta'minlaydi. Post-mitotik nazorat punkti g'ayritabiiy mitozli qiz hujayralarning keyingi interfazaga kirishiga to'sqinlik qilishi mumkin. Bu nazorat -o'tkazish punktlarining barchasi hujayra tsiklining rivojlanishi davomida genomik beqarorlikni kamaytirish uchun zarurdir.

JMCB ning joriy soni

Yuqorida aytib o'tilganidek, genomik beqarorlik va saraton o'rtasidagi munosabatlar murakkab. U hujayra va molekulyar biologiyaning deyarli barcha asosiy jihatlarini o'z ichiga oladi. Ushbu maxsus sonda biz DNKning replikatsiyasi, DNKning shikastlanishiga javob berish va tuzatish bilan bog'liq bir necha jihatlarni qamrab olish va ularning saraton kasalligiga ta'sirini ko'rsatish uchun to'qqizta sharhli maqolani to'playmiz. Muayyan mavzular quyidagilardir: to'xtab qolgan replikatsiya vilkalarini qayta ishga tushirish, litsenziyalashni takrorlash, Okazaki parchalarini pishib etish, to'xtab qolgan replikatsiya vilkalarini hal qilishda RecQ va Blm helikazalari, o'simta hosil bo'lishida RAD9 nazorat punkti oqsillari, p53 mikroRNK regulyatsiyasi, DNK shikastlanishining epigenetik regulyatsiyasi, DNK tuzatish polimorfizmi. va saraton xavfi, va o'simta va terapiya sharoitida sintetik o'lim va hayotiylik. Mitoz va hujayra tsiklini nazorat qilish punktlarini tartibga solish genom barqarorligini saqlash tizimining ajralmas qismi bo'lsa -da, bo'sh joy cheklanganligi sababli bu jihatlar bo'yicha sharhlar kiritilmagan.


Bo'limni ko'rib chiqish

Bu bobda siz butun sistemali organlarning tuzilishi va funktsiyalari haqida bilib oldingiz. Xususan, siz buni bilib oldingiz:

  • Yallig'lanish tizimi teri, soch va tirnoqlardan iborat. Yallig'lanish tizimining funktsiyalari tanani himoya qoplamasi bilan ta'minlash, atrof -muhitni sezish va gomeostazni saqlashga yordam berishdan iborat.
  • Teri va rsquosning asosiy funktsiyalari tanadan suv yo'qotilishini oldini olish, mikroorganizmlarning kirib kelishiga to'siq bo'lib xizmat qilish, D vitamini sintezi, UV nurini blokirovka qilish va tana haroratini boshqarishga yordam berishdan iborat.
  • Teri ikki xil qatlamdan iborat: epidermis deb ataladigan ingichka tashqi qatlam va dermis deb nomlangan qalinroq ichki qavat.
    • Epidermis asosan keratin hosil qiluvchi keratinotsitlar deb ataladigan epiteliya hujayralaridan iborat. Epidermisning pastki qismida yangi keratinotsitlar paydo bo'ladi. Ular keratin bilan to'lib, teri yuzasiga qarab harakatlanayotganda o'lib ketadilar, bu erda ular suv o'tkazmaydigan himoya qatlamini hosil qiladi.
    • Dermis asosan mustahkamlik va cho'zishni ta'minlaydigan qattiq biriktiruvchi to'qimalardan va deyarli barcha teri tuzilmalaridan, shu jumladan qon tomirlari, sezgi retseptorlari, soch follikulalari, yog 'va ter bezlaridan iborat.
    • Epidermisning eng ichki qatlami - bu bazal qatlam bo'lib, u yangi keratinotsitlarni hosil qilish uchun bo'linadigan ildiz hujayralarini o'z ichiga oladi. Keyingi qavat - qatlam spinosum, u eng qalin qatlam bo'lib, Langerhans hujayralari va tikanli keratinotsitlarni o'z ichiga oladi. Buning ortidan qatlam granulosumi keladi, bunda keratinotsitlar keratin bilan to'lib, o'lishni boshlaydi. Stratum lucidum keyingi, lekin faqat kaft va taglikda. U shaffof o'lik keratinotsitlardan iborat. Eng tashqi qavat - kornea qatlami, u epidermisning qolgan qismi uchun qattiq, suv o'tkazmaydigan to'siqni tashkil etuvchi, o'lik, mahkam o'ralgan keratinotsitlardan iborat.
    • Melanin - inson terisining rangini belgilaydigan asosiy pigment. Shu bilan birga, karotin va gemoglobin pigmentlari ham terining rangiga, ayniqsa melanin miqdori past bo'lgan teriga hissa qo'shadi.
    • Odatda sog'lom terining yuzasi 19 ta filadan 1000 ga yaqin turni ifodalovchi juda ko'p miqdordagi bakteriyalar bilan qoplangan. Tananing turli joylari teri mikroorganizmlari uchun turli xil yashash joylarini ta'minlaydi. Odatda, teridagi mikroorganizmlar, agar ularning muvozanati buzilmasa, bir -birini nazoratda ushlab turadilar.
    • Soch o'sishi follikulaning ichidagi ildiz hujayralari bo'linib, yangi keratinotsitlar hosil bo'lganda boshlanadi.
    • Soch tolasi uchta zonadan iborat: eng tashqi qismi kesikula deb nomlanadi, o'rta qismi korteks, ichki qismi esa medulla.

    Endi siz tananing yuzasidagi organlar haqida bilib oldingiz, keyingi bo'limni o'qib, ichkariga kiring va boshqa funktsiyalar qatorida bizni ichimizda himoya qiladigan va qo'llab -quvvatlaydigan suyak tizimi haqida bilib oling.


    Saraton hujayralari biologiyasi dasturi

    DF/HCC saraton hujayralari biologiyasi dasturi saraton patogenezini yaxshiroq tushunish va bu bilimlarni saraton terapiyasida qo'llash uchun molekulyar, biokimyoviy va hujayralarga asoslangan yondashuvlardan foydalanadi. Dastur asosiy kashfiyotlar uchun klinikada o'tkaziladigan asosiy kashfiyotlar yoki klinikada o'tkazilgan kuzatuvlarni o'z ichiga olgan hamkorlikni osonlashtiradi. Dastur ma'lum kasalliklarning klinik xususiyatlari haqida chuqur bilimga ega bo'lgan klinik va tarjima tadqiqotchilari bilan a'zolik hamkorligini rag'batlantiradi. A'zolar ko'plab hamkorlikdagi grantlarni sotib oldilar, ko'p miqdordagi qo'shma hujjatlarni chop etdilar va klinik tadqiqotchilar va farmatsevtika sanoati bilan bir nechta klinikaga qadar tadqiqotlarni boshlash uchun hamkorlik qildilar.

    Dasturning o'ziga xos maqsadlariga erishish sa'y-harakatlari saraton genomini funktsionallashtirishga qaratilgan bo'lib, uning tarkibiga saraton signalizatsiya mexanizmlarini o'rganish uchun yangi genomik ma'lumotlarga asoslangan batafsil mexanik tadqiqotlar va ularni tahlil qilishga imkon beradigan tizim darajasidagi yangi texnologiyalarni ishlab chiqish kiradi. yo'llar. Hozirgi vaqtda saraton hujayralari biologiyasi dasturining 100 dan ortiq a'zolari bor.

    DF/HCC "Ilmiy hamjamiyat" seminarlar seriyasini ulash

    DF/HCC Connect: Ilmiy seminarlar seriyasida Zoom (bu erda hisob yaratish) orqali masofadan turib qatnashish taklif etiladi, bu qiyin paytda bizning professor -o'qituvchilar, stajyorlar va laboratoriya xodimlarini birlashtirish.


    4. Erkin radikallarning inson salomatligiga zararli ta'siri

    Yuqorida aytib o'tilganidek, agar erkin radikallar va oksidlovchilar haddan ziyod oksidlovchi stress deb ataladigan hodisaga olib kelsa, bu zararli jarayon bo'lib, u membranalar, lipidlar, oqsillar, lipoproteinlar va deoksiribonuklein kislotasi (DNK) kabi bir qancha hujayrali tuzilmalarga salbiy ta'sir ko'rsatishi mumkin. [16 va#x0201321]. Oksidlanish stressi erkin radikallarning shakllanishi va hujayralarni tozalash qobiliyati o'rtasida nomutanosiblik paydo bo'lganda paydo bo'ladi. Masalan, ortiqcha gidroksil radikal va peroksinitrit lipid peroksidlanishiga olib kelishi mumkin, bu esa hujayra membranalari va lipoproteinlarga zarar etkazadi. Bu o'z navbatida malondialdegid (MDA) va konjuge dien birikmalarining paydo bo'lishiga olib keladi, ular ma'lumki, ular sitotoksik va mutagen. Radikal zanjirli reaktsiya bo'lib, lipid peroksidlanishi juda tez lipid molekulalariga ta'sir qiladi [25]. Proteinlar oksidlovchi stress tufayli zararlanishi, ularning fermentativ faolligini yo'qotishi yoki buzilishini aniqlashi mumkin bo'lgan konformatsion modifikatsiyaga uchrashi mumkin [20, 25].

    Hatto DNK ham oksidlovchi stress bilan bog'liq shikastlanishlarga moyil, ularning eng vakili 8-okso-2 va xoksioguanozin (8-OHdG) hosil bo'lishidir, bu DNKning o'ta zararli shikastlanishi bo'lib, u mutagenez uchun ham javobgar bo'lishi mumkin. Nishida va boshqalar ko'rsatgan. [26]. Bu, shuningdek, epigenetik ma'lumotlarning yo'qolishiga olib kelishi mumkin, ehtimol bu genlar targ'ibotchilaridagi CpG orolining metillanish aktivligining buzilishi bilan bog'liq [27]. Ta'kidlash joizki, Valavanidis va uning hamkasblari [28] oksidlovchi stressning biomarkeri sifatida to'qimalarda 8-OHdG darajasini taklif qilishgan. Albatta, hujayralar DNK shikastlanishiga qarshi mudofaa reaktsiyasi sifatida bazani olib tashlashni tuzatish (BER) yoki antioksidantlar kabi bir qancha mexanizmlarni o'rnatishi mumkin [17 �].

    Agar qattiq nazorat qilinmasa, oksidlovchi stress surunkali va degenerativ kasalliklarning qo'zg'atilishiga, shuningdek, tananing qarishi jarayonini tezlashtirishga va o'tkir patologiyalarga (masalan, travma va insult) olib kelishi mumkin.

    4.1. Saraton va oksidlovchi stress

    Odamlarda saraton kasalligining boshlanishi - bu murakkab jarayon bo'lib, u endogen va/yoki ekzogen tetiklar yordamida uyali va molekulyar o'zgarishlarni talab qiladi. Ma'lumki, DNKning oksidlovchi shikastlanishi saraton rivojlanishiga turtki beradigan omillardan biri hisoblanadi [14, 15, 22]. Saraton xromosoma anormalliklari va oksidlovchi stress bilan aniqlangan onkogen faollashuvi bilan qo'zg'atilishi va/yoki rag'batlantirilishi mumkin. Gidrolizlangan DNK asoslari DNK oksidlanishining yon mahsulotidir va kimyoviy kanserogenezda eng muhim voqealardan biri hisoblanadi [14, 22]. Bunday qo'shimchalarning paydo bo'lishi transkriptomik fiziologik profilni o'zgartirib, gen mutatsiyasini keltirib, hujayralarning normal o'sishiga putur etkazadi. Oksidlanish stressi, shuningdek, DNK tuzilishiga har xil miqdordagi modifikatsiyalarni keltirib chiqarishi mumkin, masalan, asos va shakarning shikastlanishi, DNK-oqsil o'zaro bog'liqliklari, iplarning uzilishi va bazasiz joylar. Masalan, tamaki chekish, atrof -muhitni ifloslantiruvchi moddalar va surunkali yallig'lanish DNKning oksidlovchi shikastlanish manbalari bo'lib, ular shish paydo bo'lishiga yordam beradi [14, 17, 29]. Turmush tarzi sabablaridan kelib chiqadigan oksidlovchi stress ham saraton kasalligining rivojlanishida muhim rol o'ynashi mumkin, chunki bu dietadagi yog'larni iste'mol qilish (organizmni lipid peroksidlanish xavfi yuqori bo'lgan omil) va saratonning har xil turlaridan o'lim darajasi o'rtasidagi kuchli bog'liqlikdan dalolat beradi. , 21].

    4.2. Yurak -qon tomir kasalliklari va oksidlovchi stress

    Yurak -qon tomir kasalliklari (KVH) - ko'p faktorli etiologiyaga ega klinik sub'ektlar bo'lib, ular odatda juda ko'p miqdordagi xavf omillari bilan bog'liq bo'lib, ularning eng keng tarqalgani giperkolesterolemiya, gipertoniya, chekish odati, diabet, muvozanatsiz ovqatlanish, stress va o'tirgan hayot [11]. , 30, 31]. So'nggi yillarda, tadqiqot ma'lumotlari shuni ko'rsatdiki, oksidlovchi stress ko'plab yurak -qon tomir kasalliklari uchun asosiy yoki ikkilamchi sabab bo'lishi kerak [18]. Oksidlanish stressi asosan aterosklerozning qo'zg'atuvchisi vazifasini bajaradi. Ma'lumki, ateromatoz blyashka shakllanishi endoteliyning erta yallig'lanishidan kelib chiqadi, bu esa o'z navbatida joyida to'plangan makrofaglar tomonidan ROS hosil bo'lishiga olib keladi. Keyin aylanma LDL reaktiv kislorod turlari bilan oksidlanadi, natijada ko'pikli hujayralar paydo bo'ladi va lipidlar to'planadi. Bu hodisalarning natijasi - aterosklerotik blyashka hosil bo'lishi. In vivo va ex vivo tadqiqotlar ateroskleroz, ishemiya, gipertoniya, kardiyomiyopatiya, yurak gipertrofiyasi va konjestif yurak etishmovchiligida oksidlovchi stressning rolini tasdiqlovchi dalillar keltirdi [11, 16, 30, 31].

    4.3. Nevrologik kasallik va oksidlovchi stress

    Oksidlanish stressi bir qancha nevrologik kasalliklar bilan bog'liq (masalan, Parkinson kasalligi, Altsgeymer kasalligi (AD), amyotrofik lateral skleroz (ALS), ko'p skleroz, depressiya va xotira yo'qolishi) [32 �]. Miloddan avvalgi bir qancha eksperimental va klinik tadqiqotlar shuni ko'rsatdiki, oksidlovchi shikastlanish neyronlarning yo'qolishida va demensiyaning rivojlanishida asosiy rol o'ynaydi [34]. β-amiloid, zaharli peptid, tez -tez AD bemorlarining miyasida uchraydi, erkin radikal ta'sirida ishlab chiqariladi va ma'lum bo'lishicha, hech bo'lmaganda ADning boshlanishi va rivojlanishida kuzatilgan neyrodejeneratsiya uchun javobgardir [35].

    4.4. Nafas olish kasalligi va oksidlovchi stress

    Bir qator tadqiqotlar shuni ko'rsatdiki, o'pka kasalliklari, masalan, astma va surunkali obstruktiv o'pka kasalligi (KOAH), tizimli va mahalliy surunkali yallig'lanish bilan aniqlanadi, oksidlovchi stress bilan bog'liq [36 �]. Oksidantlar NF-kappa B va AP-1 kabi yo'llar va transkripsiya omillarini o'z ichiga olgan turli kinazalarni faollashtirish orqali yallig'lanishni kuchaytirishi ma'lum [38, 39].

    4.5. Romatoid artrit va oksidlovchi stress

    Romatoid artrit - bu bo'g'imlarga va atrofdagi to'qimalarga ta'sir qiluvchi surunkali yallig'lanish kasalligi bo'lib, makrofaglar va faollashgan T hujayralari infiltratsiyasi bilan ajralib turadi [15, 40, 41]. Yallig'lanish joyidagi erkin radikallar bu sindromning boshlanishida ham, rivojlanishida ham muhim rol o'ynaydi, bu ta'sirlangan bemorlarning sinovial suyuqligida izoprostan va prostaglandin darajasining oshishi bilan namoyon bo'ladi [41].

    4.6. Buyrak kasalliklari va oksidlovchi stress

    Oksidlanish stressi glomerulo- va tubulalar-interstitsial nefrit, buyrak etishmovchiligi, proteinuriya va uremiya kabi buyrak apparatlariga ta'sir qiladigan ko'plab kasalliklarda ishtirok etadi [16, 42]. Buyraklarga oksidlanish stressi salbiy ta'sir ko'rsatadi, chunki ROS ishlab chiqarish yallig'lanish hujayralari va proinflamatuar sitokin ishlab chiqarishni rag'batlantiradi, bu yallig'lanishning dastlabki bosqichiga olib keladi. Ushbu erta bosqichda yallig'lanish vositachilari sifatida TNF-alfa va IL-1b, shuningdek NF- asosiy rol o'ynaydi.κYallig'lanish jarayonini davom ettirish uchun zarur bo'lgan transkripsiya omili sifatida B. Oxirgi bosqich hujayradan tashqari matritsa sintezini boshqaruvchi TGF-beta ishlab chiqarishning ko'payishi bilan tavsiflanadi. Shunday qilib, oksidlovchi stress stimullari buyrak to'qimalariga surunkali ta'sir ko'rsatsa, natijalar yallig'lanishning dastlabki bosqichi bo'ladi va keyinchalik buyrak etishmovchiligiga olib keladigan organlar faoliyatini buzadigan ko'p miqdordagi fibrotik to'qima hosil bo'ladi. Siklosporin, takrolimus, gentamitsin va bleomitsin kabi ba'zi dorilar nefrotoksikdir, chunki ular lipid peroksidlanish orqali erkin radikallar va oksidlanish stressini oshiradi [42 �]. Og'ir (Cd, Hg, Pb va As) va o'tish metallari (Fe, Cu, Co va Cr), kuchli oksidlovchi stress induktorlari sifatida, nefropatiyaning har xil shakllari uchun, shuningdek, saratonning ayrim turlari uchun javobgardir [22. , 23].

    4.7. Jinsiy kamolot va oksidlovchi stress

    Bir nechta mualliflar, oksidlovchi stress kechiktirilgan jinsiy etuklik va balog'atga etishishning boshlanishi uchun sabab bo'lishi mumkinligini ta'kidladilar [46, 47]. Bu tug'ruqdan oldingi yoshdagi bolalar erkin radikallar va oksidlanish stressining ko'payishi uchun javobgar bo'lgan, shuningdek homilador ayollar bir xil metall elementga duchor bo'lganida, Cd ta'siriga duch kelganda rost ko'rinadi.

    Xulosa qilib shuni aytishimiz mumkinki, oksidlovchi stress va erkin radikallar turli to'qimalar va tizimlarga ta'sir etuvchi bir qancha patologik sharoitlar uchun mas'ul bo'lib, inson salomatligiga eng muhim va keng tarqalgan zararlardan biri hisoblanadi.


    Kurs tavsifi

    Bu kurs MIT -ning biologiya bo'limi tomonidan taklif etiladigan ko'plab bakalavriat seminarlaridan biridir. Bu seminarlar yuqori darajadagi interaktiv muhitda hozirgi biologik tadqiqotlarni muhokama qilish va o'rganish uchun birlamchi tadqiqot adabiyotlaridan foydalanishga qiziqqan talabalarga mo'ljallangan.

    1971 yilda Prezident Nikson "Saratonga qarshi urush" ni e'lon qildi, ammo o'ttiz yildan keyin ham urush davom etmoqda. Biz urushda g'alaba qozonish yo'lida qancha yutuqlarga erishdik va kurashni yaxshilash uchun nima qilyapmiz? Shish paydo bo'lishi, rivojlanishi va metastaz bilan bog'liq molekulyar va uyali hodisalarni tushunish saraton kasallari uchun innovatsion terapiyani ishlab chiqish uchun hal qiluvchi ahamiyatga ega. Xamirturush, C. elegans, sichqonlar va hujayra madaniyati modellarida biokimyoviy, molekulyar va genetik tahlillar yordamida asosiy tadqiqotlar orqali bu jarayonlar haqidagi tushunchalar aniqlandi. Biz saraton kasalligini o'rganish uchun ishlatiladigan laboratoriya asboblari va usullarini, saraton biologiyasidagi asosiy kashfiyotlarni va bu yutuqlarning tibbiy ta'sirini o'rganamiz. Saraton kasalligiga turli xil yondashuvlarning kuchli va cheklangan tomonlarini tushunishga yordam beradigan asosiy adabiyotlarni tanqidiy tahlil qilish darsning diqqat markazida bo'ladi. Model organizmlarida o'tkazilgan saraton tadqiqotlarining klinik oqibatlari va bu halokatli kasallik bilan kurashni tugatish istiqbollariga alohida e'tibor qaratiladi.


    Asosiy eksizyonlarni ta'mirlash va nukleotidlarni olib tashlash

    Base excision repair (BER) involves multiple enzymes to excise and replace a single damaged nucleotide base. The base modifications primarily repaired by BER enzymes are those damaged by endogenous oxidation and hydrolysis. A DNA glycosylase cleaves the bond between the nucleotide base and ribose, leaving the ribose phosphate chain of the DNA intact but resulting in an apurinic or apyrimidinic (AP) site. 8-Oxoguanine DNA glycosylase I (Ogg1) removes 7,8-dihydro-8-oxoguanine (8-oxoG), one of the base mutations generated by reactive oxygen species. Polymorphism in the human OGG1 gene is associated with the risk of various cancers such as lung and prostate cancer. Uracil DNA glycosylase, another BER enzyme, excises the uracil that is the product of cytosine deamination, thereby preventing the subsequent C→T point mutation. 15 N-Methylpurine DNA glycosylase (MPG) is able to remove a variety of modified purine bases. 16

    The AP sites in the DNA that result from the action of BER enzymes, as well as those that result from depyrimidination and depurin ation actions, are repaired by the action of AP-endonuclease 1 (APE1). APE1 cleaves the phosphodiester chain 5’ to the AP site. The DNA strand then contains a 3’-hydroxyl group and a 5’-abasic deoxyribose phosphate. DNA polymerase β (Polβ) inserts the correct nucleotide based on the corresponding W-C pairing and removes the deoxyribose phosphate through its associated AP-lyase activity. The presence of X-ray repair cross-complementing group 1 (XRCC1) is necessary to form a heterodimer with DNA ligase III (LIG3). XRCC1 acts as a scaffold protein to present a non-reactive binding site for Polβ, and bring the Polβ and LIG3 enzymes together at the site of repair. 17 Poly(ADP-ribose) polymerase (PARP-1) interacts with XRCC1 and Polβ and is a necessary component of the BER pathway. 18,19 The final step in the repair is performed by LIG3, which connects the deoxyribose of the replacement nucleotide to the deoxyribosylphosphate backbone. This pathway has been named “short-patch BER”. 20

    An alternative pathway called “long-patch BER” replaces a strand of nucleotides with a minimum length of 2 nucleotides. Repair lengths of 10 to 12 nucleotides have been reported. 21,22 Longpatch BER requires the presence of proliferation cell nuclear antigen (PCNA), which acts as a scaffold protein for the restructuring enzymes. 23 Other DNA polymerases, possibly Polδ and Polε, 24 are used to generate an oligonucleotide flap. The existing nucleotide sequence is removed by flap endonuclease-1 (FEN1). The oligonucleotide is then ligated to the DNA by DNA ligase I (LIG1), sealing the break and completing the repair. 17 The process used to determine the selection of short-patch versus long patch BER pathways is still under investigation (4 -rasm). 25

    4 -rasm. Schematic of both short-patch and long-patch BER pathways.

    While BER may replace multiple nucleotides via the long-patch pathway, the initiating event for both short-patch and long-patch BER is damage to a single nucleotide, resulting in minimal impact on the structure of the DNA double helix. Nucleotide excision repair (NER) repairs damage to a nucleotide strand containing at least 2 bases and creating a structural distortion of the DNA. NER acts to repair single strand breaks in addition to serial damage from exogenous sources such as bulky DNA adducts and UV radiation. 26 The same pathway may be used to repair damage from oxidative stress. 27 Over 20 proteins are involved in the NER pathway in mammalian cells, including XPA, XPC-hHR23B, replication protein A (RPA), transcription factor TFIIH, XPB and XPD DNA helicases, ERCC1-XPF and XPG, Polδ, Polε, PCNA, and replication factor C. 28 Overexpression of the excision repair cross-complementing (ERCC1) gene has been associated with cisplatin resistance by non-small-cell lung cancer cells 29 and corresponds to enhanced DNA repair capacity. 30 Global genomic NER (GGR) repairs damage throughout the genome, while a specific NER pathway called Transcription Coupled Repair (TCR) repairs genes during active RNA polymerase transcription. 31


    Tarkibi

    • Physical agents such as heat or radiation can damage a cell by literally cooking or coagulating their contents.
    • Impaired nutrient supply, such as lack of oxygen or glucose, or impaired production of adenosine triphosphate (ATP) may deprive the cell of essential materials needed to survive. [3]
    • Metabolic: Hypoxia and Ischemia
    • Chemical Agents
    • Microbial Agents
    • Immunologic Agents: Allergy and autoimmune diseases such as Parkinson's and Alzehimers disease.
    • Genetic factors: Such as Down's syndrome and sickle cell anemia [4]

    The most notable components of the cell that are targets of cell damage are the DNA and the cell membrane.

      : In human cells, both normal metabolic activities and environmental factors such as ultraviolet light and other radiations can cause DNA damage, resulting in as many as one million individual molecular lesions per cell per day. [5]
  • Membrane damage: damage to the cell membrane disturbs the state of cell electrolytes, e.g. calcium, which when constantly increased, induces apoptosis.
  • Mitochondrial damage: May occur due to ATP decrease or change in mitochondrial permeability.
  • Ribosome damage: Damage to ribosomal and cellular proteins such as protein misfolding, Leading to apoptotic enzyme activation.
  • Some cell damage can be reversed once the stress is removed or if compensatory cellular changes occur. Full function may return to cells but in some cases a degree of injury will remain. [ iqtibos kerak ]

    Reversible Edit

    Cellular swelling Edit

    Cellular swelling (or cloudy swelling) may occur due to cellular hypoxia, which damages the sodium-potassium membrane pump it is reversible when the cause is eliminated. [6] Cellular swelling is the first manifestation of almost all forms of injury to cells. When it affects many cells in an organ, it causes some pallor, increased turgor, and increase in weight of the organ. On microscopic examination, small clear vacuoles may be seen within the cytoplasm these represent distended and pinched-off segments of the endoplasmic reticulum. This pattern of non-lethal injury is sometimes called hydropic change or vacuolar degeneration. [7] Hydropic degeneration is a severe form of cloudy swelling. It occurs with hypokalemia due to vomiting or diarrhea.

    The ultrastructural changes of reversible cell injury include:

    Fatty change Edit

    The cell has been damaged and is unable to adequately metabolize fat. Small vacuoles of fat accumulate and become dispersed within cytoplasm. Mild fatty change may have no effect on cell function however more severe fatty change can impair cellular function. In the liver, the enlargement of hepatocytes due to fatty change may compress adjacent bile canaliculi, leading to cholestasis. Depending on the cause and severity of the lipid accumulation, fatty change is generally reversible. Fatty Change is also known as fatty degeneration, fatty metamorphosis, or fatty steatosis.

    Irreversible Edit

    Necrosis Edit

    Necrosis is characterised by cytoplasmic swelling, irreversible damage to the plasma membrane, and organelle breakdown leading to cell death. [8] The stages of cellular necrosis include pyknosis clumping of chromosomes and shrinking of the nucleus of the cell, karyorrhexis fragmentation of the nucleus and break up of the chromatin into unstructured granules, and karyolysis dissolution of the cell nucleus. [9] Cytosolic components that leak through the damaged plasma membrane into the extracellular space can incur an inflammatory response. [10]

    There are six types of necrosis: [11]

    • Coagulative necrosis
    • Liquefactive necrosis
    • Caseous necrosis
    • Fat necrosis
    • Fibroid necrosis
    • Gangrenous necrosis

    Apoptozni tahrirlash

    Apoptosis is the programmed cell death of superfluous or potentially harmful cells in the body. It is an energy dependent process mediated by proteolytic enzymes called caspases, which trigger cell death through the cleaving of specific proteins in the cytoplasm and nucleus. [12] The dying cells shrink and condense into apoptotic bodies. The cell surface is altered so as to display properties which lead to rapid phagocytosis by macrophages or neighbouring cells. [12] Unlike necrotic cell death, neighbouring cells are not damaged by apoptosis as cytosolic products are safely isolated by membranes prior to undergoing phagocytosis. [10] In the average adult between 50 and 70 billion cells die each day due to apoptosis. Inhibition of apoptosis can result in a number of cancers, autoimmune diseases, inflammatory diseases, and viral infections. Hyperactive apoptosis can lead to neurodegenerative diseases, hematologic diseases, and tissue damage.

    When a cell is damaged the body will try to repair or replace the cell to continue normal functions. If a cell dies the body will remove it and replace it with another functioning cell, or fill the gap with connective tissue to provide structural support for the remaining cells. The motto of the repair process is to fill a gap caused by the damaged cells to regain structural continuity. Normal cells try to regenerate the damaged cells but this cannot always happen. Asexual reproduction is what repairs cells

    Regeneration Edit

    Regeneration of parenchyma cells, or the functional cells, of an organism. The body can make more cells to replace the damaged cells keeping the organ or tissue intact and fully functional.

    Replacement Edit

    When a cell cannot be regenerated the body will replace it with stromal connective tissue to maintain tissue/organ function. Stromal cells are the cells that support the parenchymal cells in any organ. Fibroblasts, immune cells, pericytes, and inflammatory cells are the most common types of stromal cells. [13]

    ATP (adenosine triphosphate) depletion is a common biological alteration that occurs with cellular injury. This change can happen despite the inciting agent of the cell damage. A reduction in intracellular ATP can have a number of functional and morphologic consequences during cell injury. These effects include:

    • Failure of the ATP dependent pumps ( Na +
      /K +
      pump and Ca 2+
      pump), resulting in a net influx of Na +
      and Ca 2+
      ions and osmotic swelling.
    • ATP-depleted cells begin to undertake anaerobic metabolism to derive energy from glycogen which is known as 'glycogenolysis'.
    • A consequent decrease in the intracellular pH of the cell arises, which mediates harmful enzymatic processes.
    • Early clumping of nuclear chromatin then occurs, known as 'pyknosis', and leads to eventual cell death. [14]

    DNK shikastlanishi tahrirlash

    DNA damage (or RNA damage in the case of some virus genomes) appears to be a fundamental problem for life. As noted by Haynes, [15] the subunits of DNA are not endowed with any peculiar kind of quantum mechanical stability, and thus DNA is vulnerable to all the "chemical horrors" that might befall any such molecule in a warm aqueous medium. These chemical horrors are DNA damages that include various types of modification of the DNA bases, single- and double-strand breaks, and inter-strand cross-links (see DNA damage (naturally occurring). DNA damages are distinct from mutations although both are errors in the DNA. Whereas DNA damages are abnormal chemical and structural alterations, mutations ordinarily involve the normal four bases in new arrangements. Mutations can be replicated, and thus inherited when the DNA replicates. In contrast, DNA damages are altered structures that cannot, themselves, be replicated.

    Several different repair processes can remove DNA damages (see chart in DNA repair). However, those DNA damages that remain un-repaired can have detrimental consequences. DNA damages may block replication or gene transcription. These blockages can lead to cell death. In multicellular organisms, cell death in response to DNA damage may occur by a programmed process, apoptosis. [16] Alternatively, when a DNA polymerase replicates a template strand containing a damaged site, it may inaccurately bypass the damage and, as a consequence, introduce an incorrect base leading to a mutation. Experimentally, mutation rates increase substantially in cells defective in DNA mismatch repair [17] [18] or in Homologous recombinational repair (HRR). [19]

    In both prokaryotes and eukaryotes, DNA genomes are vulnerable to attack by reactive chemicals naturally produced in the intracellular environment and by agents from external sources. An important internal source of DNA damage in both prokaryotes and eukaryotes is reactive oxygen species (ROS) formed as byproducts of normal aerobic metabolism. For eukaryotes, oxidative reactions are a major source of DNA damage (see DNA damage (naturally occurring) and Sedelnikova et al. [20] ). In humans, about 10,000 oxidative DNA damages occur per cell per day. [21] In the rat, which has a higher metabolic rate than humans, about 100,000 oxidative DNA damages occur per cell per day. In aerobically growing bacteria, ROS appear to be a major source of DNA damage, as indicated by the observation that 89% of spontaneously occurring base substitution mutations are caused by introduction of ROS-induced single-strand damages followed by error-prone replication past these damages. [22] Oxidative DNA damages usually involve only one of the DNA strands at any damaged site, but about 1–2% of damages involve both strands. [23] The double-strand damages include double-strand breaks (DSBs) and inter-strand crosslinks. For humans, the estimated average number of endogenous DNA DSBs per cell occurring at each cell generation is about 50. [24] This level of formation of DSBs likely reflects the natural level of damages caused, in large part, by ROS produced by active metabolism.

    Repair of DNA damages Edit

    Five major pathways are employed in repairing different types of DNA damages. These five pathways are nucleotide excision repair, base excision repair, mismatch repair, non-homologous end joining and homologous recombinational repair (HRR) (see chart in DNA repair) and reference. [16] Only HRR can accurately repair double strand damages, such as DSBs. The HRR pathway requires that a second homologous chromosome be available to allow recovery of the information lost by the first chromosome due to the double-strand damage.

    DNA damage appears to play a key role in mammalian aging, and an adequate level of DNA repair promotes longevity (see DNA damage theory of aging and reference. [25] ). In addition, an increased incidence of DNA damage and/or reduced DNA repair cause an increased risk of cancer (see Cancer, Carcinogenesis and Neoplasm) and reference [25] ). Furthermore, the ability of HRR to accurately and efficiently repair double-strand DNA damages likely played a key role in the evolution of sexual reproduction (see Evolution of sexual reproduction and reference). [ iqtibos kerak ] In extant eukaryotes, HRR during meiosis provides the major benefit of maintaining fertility. [ iqtibos kerak ]


    Teaching Cell Biology and Genetics Using Cancer

    This playlist can be used to teach several core topics in cell biology and genetics by connecting students with case studies and multimedia resources about cancer. The topics covered include the cell cycle, cancer, biotechnology, and genetic disease.

    By completing the resources in this playlist, students will be able to:

    • Explain the steps and regulation of the cell cycle.
    • Interpret data to explain the role of tumor suppressors in cell cycle regulation.
    • Predict which gene mutations cause cancer. Compare and contrast oncogenes and tumor suppressor genes in particular.
    • Use evidence to support the following claims:
      • Cancer is typically caused by mutations in several genes.
      • Mutations in the same genes can be involved in the development of different types of cancers (i.e., breast cancer or lung cancer).
      • Mutations in different genes can cause the same type of cancer.

      This playlist can be used in undergraduate biology courses. Implementing this playlist should take about 200 minutes of class time in total, spread out among other discussions and activities.


      Videoni tomosha qiling: Saratonni 3 daqiqada davolash mumkin! (Yanvar 2022).