Mechanism ntawm cov txheej txheem apoptosis

Cov txheej txheem ntawm apoptosis tuaj yeem raug faib ua ntu ntu hauv qab no:

Tau txais apoptosis teeb liab → kev sib cuam tshuam ntawm apoptosis regulating molecules → activation ntawm proteolytic enzyme (Caspase) → nkag mus rau hauv cov txheej txheem nruam cov tshuaj tiv thaiv

Pib theem

Qhov pib ntawm apoptosis yog qhov qhib lossis kaw ntawm cov kev hloov pauv hauv cov xovtooj tom qab lub xovtooj ntawm tes pom tau tias muaj cov teeb liab sib cuam tshuam. Cov xwm txheej sab nraud sib txawv pib apoptosis nyob rau hauv ntau txoj kev, ua rau sib txawv teeb liab transduction. Objectively hais lus, kev nkag siab ntawm lub teeb liab kis tau tus mob nyob rau hauv tus txheej txheem ntawm cell apoptosis yog tseem tsis tiav. Txoj kev pom tseeb dua yog:

1) Membrane receptor pathway ntawm cell apoptosis: ntau yam sab nraud yog cov pib ntawm cell apoptosis. Lawv tuaj yeem xa cov teeb liab apoptosis los ntawm cov teeb liab sib txawv thiab ua rau cov cell apoptosis. Cia peb coj Fas FasL ua piv txwv:

Fas yog transmembrane protein, uas belongs rau cov qog necrosis yam receptor superfamily. Nws tuaj yeem pib lub teeb liab apoptosis hloov pauv thiab ua rau cell apoptosis los ntawm kev khi nrog FasL. Nws qhov kev ua kom muaj xws li cov kauj ruam: ua ntej, lub ligand induces trimerization ntawm lub receptor, thiab tom qab ntawd tsim ib qho apoptosis inducing complex ntawm lub cell membrane, uas muaj xws li cov Fas muaj feem xyuam rau cov protein FADD nrog rau cov neeg tuag. Fas, tseem hu ua CD95, yog ib qho receptor molecule uas muaj 325 amino acids. Thaum Fas khi rau ligand FasL, nws tuaj yeem pib ua kom tuag teeb liab hloov mus los ntawm Fas molecules, nws thiaj li ua rau muaj kev hloov pauv hauv cov hlwb thiab kev tuag ntawm tes. Raws li kev nthuav qhia thoob ntiaj teb receptor molecule, Fas tuaj yeem tshwm sim ntawm ntau hom hlwb, tab sis qhov kev qhia ntawm FasL muaj nws tus yam ntxwv. Nws feem ntau tsuas yog tshwm sim hauv T cells thiab NK hlwb. Yog li, activated killer immune cells tuaj yeem tua cov hom phiaj los ntawm apoptosis. Lub intracellular ntu ntawm Fas molecule muaj qhov tshwj xeeb tuag domain (DD). Tom qab kev sib xyaw ua ke ntawm trimeric Fas thiab FasL, qhov kev tuag ntawm peb Fas molecules yog pawg, nyiam lwm cov protein FADD nrog tib qhov kev tuag nyob hauv cytoplasm. FADD yog connexin nyob rau hauv kev tuag teeb liab transcription, uas muaj ob ntu: lub C davhlau ya nyob twg (DD sau) thiab N davhlau ya nyob twg (DED). DD domain yog lub luag haujlwm rau kev khi nrog DD sau ntawm ntu ntu ntawm Fas molecule. Cov protein tom qab ntawd txuas lwm qhov txuas ntxiv nrog DED nrog DED, uas ua rau N-seg DED tam sim ntawd hla kev txuas nrog cov tsis muaj zog caspase 8 zymogen, polymerizing ntau caspase 8 molecules. Lub caspase 8 molecule yog ces hloov los ntawm ib tug tib saw zymogen mus rau ib tug active ob chav saw protein, ua rau ib tug tom ntej cascade cov tshuaj tiv thaiv, xws li caspases, tom kawg yog activated raws li ib tug zymogen, ua rau cov nram qab no cascade cov tshuaj tiv thaiv. Apoptosis tshwm sim. Yog li ntawd, txoj kev apoptosis tshwm sim los ntawm TNF zoo ib yam li qhov no

2) Biochemical txoj kev ntawm cytochrome C tso tawm thiab Caspases ua kom

Mitochondria yog lub chaw tswj hwm ntawm cov haujlwm ntawm tes. Lawv tsis tsuas yog qhov chaw nruab nrab ntawm cov kab mob ua pa ntawm tes thiab oxidative phosphorylation, tab sis kuj yog qhov chaw ntawm cell apoptosis txoj cai. Cov txiaj ntsig tau pom tias kev tso tawm ntawm cytochrome C los ntawm mitochondria yog cov kauj ruam tseem ceeb ntawm apoptosis. Cytochrome C tso tawm rau hauv cytoplasm tuaj yeem ua ke nrog apoptosis ntsig txog yam 1 (Apaf-1) nyob rau hauv lub xub ntiag ntawm dATP los tsim ib lub polymer, thiab txhawb nqa caspase-9 los ua ke nrog nws los tsim lub cev apoptotic. Caspase-9 tau qhib, thiab qhib lub caspase-9 tuaj yeem qhib tau lwm cov caspases, xws li caspase-3, kom induce apoptosis. Tsis tas li ntawd, mitochondria kuj tso tawm apoptosis inducing yam, xws li AIF, uas koom rau hauv kev ua kom cov caspase. Nws tuaj yeem pom tau tias muaj feem cuam tshuam ntawm lub cev apoptotic muaj nyob hauv ntau qhov chaw ntawm lub cev ib txwm muaj. Apoptosis txhawb nqa yam tuaj yeem ua rau kev tso tawm ntawm cytochrome C thiab tsim lub cev apoptotic. Obviously, txoj cai ntawm cytochrome C tso tawm los ntawm mitochondria yog ib qho teeb meem tseem ceeb nyob rau hauv txoj kev tshawb no ntawm molecular mechanism ntawm apoptosis. Feem ntau apoptosis stimulating yam ua rau lub apoptosis txoj kev los ntawm mitochondria. Nws ntseeg tau tias cytochrome C tseem tso tawm los ntawm mitochondria los ntawm receptor mediated apoptosis. Piv txwv li, nyob rau hauv lub hlwb teb rau Fas, ib hom 1 cell (hom 1) muaj txaus caspase 8, uas tuaj yeem ua rau cov neeg tuag tuag ua rau apoptosis. Kev nthuav qhia ntau dhau ntawm Bcl-2 hauv cov hlwb no tsis cuam tshuam Fas induced apoptosis. Hauv lwm hom hlwb (hom2 2), xws li hepatocytes, kev ua kom cov caspase 8 kho los ntawm Fas receptor tsis tuaj yeem ncav cuag qib siab heev. Yog li ntawd, apoptotic teeb liab nyob rau hauv xws li hlwb yuav tsum tau amplified los ntawm apoptotic mitochondrial txoj kev, thiab Bid, ib tug Bcl -2 tsev neeg cov protein uas muaj tsuas yog BH3 domain, yog tus xa xov uas xa cov teeb liab apoptotic los ntawm cystolysis enzyme 8 mus rau mitochondria. .