Cov txheej txheem uas lub xovtooj ntawm tes tuaj yeem tua nws tus kheej yog hu ua programmed cell death (PCD). Cov txheej txheem no muaj ntau ntau yam thiab ua lub luag haujlwm tseem ceeb hauv lub cev ntawm ntau yam kab mob, tshwj xeeb tshaj yog cov cellular. Feem ntau thiab kawm tau zoo ntawm CHF yog apoptosis.
Dab tsi yog apoptosis
Apoptosis yog cov txheej txheem tswj lub cev ntawm tes ntawm tus kheej kev puas tsuaj, uas yog qhov kev puas tsuaj zuj zus thiab kev tawg ntawm nws cov ntsiab lus nrog kev tsim ntawm daim nyias nyias vesicles (apoptotic lub cev), uas tom qab absorbed los ntawm phagocytes. Cov txheej txheem caj ces no tau qhib los ntawm kev cuam tshuam ntawm qee yam sab hauv lossis sab nraud.
Nrog qhov kev tuag ntawm qhov sib txawv no, cov ntsiab lus ntawm tes tsis mus dhau ntawm daim nyias nyias thiab tsis ua rau mob. Dysregulation ntawm apoptosis ua rau mob hnyav xws li kev tswj tsis tau ntawm tes los yog cov ntaub so ntswg degeneration.
Apoptosis tsuas yog ib qho ntawm ntau hom kev ua haujlwm ntawm tes tuag (PCD), yog li nws yog qhov yuam kev los txheeb xyuas cov ntsiab lus no. Rau lub npe nrovhom kev puas tsuaj ntawm cellular kuj muaj xws li mitotic kev puas tsuaj, autophagy, thiab programmed necrosis. Lwm yam txheej txheem ntawm PCG tseem tsis tau kawm.
Cas of cell apoptosis
Yog vim li cas thiaj ua rau cov txheej txheem ntawm kev ua haujlwm ntawm tes tuag tuaj yeem yog ob qho tib si cov txheej txheem physiological thiab kev hloov pauv pathological tshwm sim los ntawm qhov tsis xws luag sab hauv lossis raug rau lwm yam tsis zoo.
Ib txwm, apoptosis sib npaug ntawm cov txheej txheem ntawm tes faib, tswj lawv tus lej thiab txhawb cov ntaub so ntswg rov ua dua tshiab. Hauv qhov no, qhov ua rau HGC yog qee cov cim qhia uas yog ib feem ntawm kev tswj hwm homeostasis. Nrog kev pab los ntawm apoptosis, cov hlwb pov tseg lossis cov hlwb uas tau ua tiav lawv txoj haujlwm raug rhuav tshem. Yog li, cov ntsiab lus ntxiv ntawm leukocytes, neutrophils thiab lwm cov ntsiab lus ntawm kev tiv thaiv kab mob ntawm tes tom qab qhov kawg ntawm kev sib ntaus sib tua raug tshem tawm vim yog apoptosis.
Txoj kev tuag yog ib feem ntawm lub voj voog ntawm lub cev ntawm lub cev xeeb tub. Apoptosis koom nrog cov txheej txheem oogenesis, thiab tseem ua rau lub qe tuag thaum tsis muaj fertilization.
Ib qho piv txwv classic ntawm kev koom tes ntawm cell apoptosis nyob rau hauv lub neej voj voog ntawm vegetative systems yog lub caij nplooj zeeg nplooj poob. Lo lus nws tus kheej los ntawm Greek lo lus apoptosis, uas txhais tau tias "poob".
Apoptosis plays lub luag haujlwm tseem ceeb hauv embryogenesis thiab ontogenesis, thaum cov ntaub so ntswg hloov hauv lub cev thiab qee yam kabmob atrophy. Ib qho piv txwv yog qhov ploj ntawm daim nyias nyias ntawm cov ntiv tes ntawm cov ceg tawv ntawm qee cov tsiaj los yog kev tuag ntawm tus Tsov tus tw thaum lub sij hawm metamorphosis.qav.
Apoptosis tuaj yeem tshwm sim los ntawm kev sib sau ntawm cov kev hloov pauv hauv lub cell uas tshwm sim los ntawm kev hloov pauv, kev laus, lossis kev ua yuam kev mitotic. Ib qho chaw tsis zoo (tsis muaj cov as-ham, tsis muaj oxygen) thiab cov kab mob sab nraud cuam tshuam los ntawm cov kab mob, cov kab mob, cov co toxins, thiab lwm yam tuaj yeem yog vim li cas rau kev tso tawm CHC. Muaj sij hawm los ua kom tiav cov txheej txheem apoptosis thiab tuag vim qhov kev loj hlob ntawm cov txheej txheem pathological - necrosis.
Morphological thiab structural-biochemical hloov pauv hauv lub cell thaum apoptosis
Cov txheej txheem ntawm apoptosis yog tus cwj pwm los ntawm qee qhov kev hloov pauv ntawm morphological, uas tuaj yeem pom tau los ntawm kev tsom xam hauv cov ntaub so ntswg npaj hauv vitro.
Cov yam ntxwv tseem ceeb ntawm cell apoptosis suav nrog:
- rebuilding the cytoskeleton;
- seal cell content;
- chromatin condensation;
- tub ntxhais fragmentation;
- cell ntim txo;
- wrinkling ntawm daim nyias nyias contour;
- npuas tsim ntawm lub xovtooj ntawm tes,
- kev puas tsuaj ntawm organelles.
Hauv cov tsiaj, cov txheej txheem no ua tiav hauv kev tsim cov apoptocytes, uas tuaj yeem cuam tshuam los ntawm ob qho tib si macrophages thiab cov hlwb nyob sib ze. Hauv cov nroj tsuag, kev tsim ntawm apoptotic lub cev tsis tshwm sim, thiab tom qab degradation ntawm protoplast, lub cev pob txha tseem nyob hauv.cell phab ntsa.
Ntxiv rau qhov kev hloov pauv morphological, apoptosis yog nrog los ntawm ntau qhov kev hloov kho ntawm qib molecular. Muaj kev nce hauv lipase thiab nuclease kev ua ub no, uas ua rau kev tawg ntawm chromatin thiab ntau cov proteins. Cov ntsiab lus ntawm cAMP sharply nce, cov qauv ntawm cov cell membrane hloov. Hauv cov nroj tsuag, kev tsim cov vacuoles loj heev tau pom.
Apoptosis txawv li cas ntawm necrosis
Qhov sib txawv tseem ceeb ntawm apoptosis thiab necrosis nyob rau hauv qhov ua rau ntawm cell degradation. Hauv thawj kis, qhov chaw ntawm kev puas tsuaj yog cov cuab yeej molecular ntawm lub cell nws tus kheej, uas ua haujlwm nyob rau hauv kev tswj hwm nruj thiab xav tau kev siv nyiaj ntawm ATP lub zog. Nrog necrosis, passive cessation ntawm lub neej tshwm sim vim muaj kev puas tsuaj sab nraud.
Apoptosis yog txheej txheem physiological uas tsim los hauv txoj hauv kev kom tsis txhob ua phem rau cov hlwb nyob ib puag ncig. Necrosis yog ib qho tshwm sim tsis muaj kev tswj hwm pathological uas tshwm sim los ntawm kev raug mob hnyav. Yog li ntawd, nws tsis yog qhov xav tsis thoob tias cov txheej txheem, morphology, thiab qhov tshwm sim ntawm apoptosis thiab necrosis yog nyob rau ntau qhov sib txawv. Txawm li cas los xij, kuj muaj qhov sib xws.
| txheej txheem yam ntxwv | Apoptosis | Necrosis |
| cell ntim | nce | |
| membrane kev ncaj ncees | violated | |
| txheej txheem mob | missing | develops |
| ATP zog | kev siv nyiaj | tsis siv |
| chromatin fragmentation | muaj | present |
| poob qis hauv ATP concentration | yog | yog |
| qhov tshwm sim ntawm txheej txheem | phagocytosis | tso tawm cov ntsiab lus rau hauv qhov chaw sib txuas |
Nyob rau hauv cov ntaub ntawv ntawm kev puas tsuaj, lub hlwb ua rau lub mechanism ntawm programmed tuag, nrog rau kev tiv thaiv necrotic kev loj hlob. Txawm li cas los xij, cov kev tshawb fawb tsis ntev los no tau pom tias muaj lwm yam uas tsis yog-pathological ntawm necrosis, uas tseem hu ua PCD.
Kev lom neeg tseem ceeb ntawm apoptosis
Txawm tias muaj qhov tseeb tias apoptosis ua rau kev tuag ntawm tes, nws lub luag haujlwm hauv kev tswj hwm kev ua haujlwm ntawm tag nrho cov kabmob yog qhov zoo heev. Cov haujlwm physiological hauv qab no yog ua los ntawm cov txheej txheem ntawm PCG:
- tuav qhov sib npaug ntawm cell proliferation thiab tuag;
- hloov kho cov ntaub so ntswg thiab lub cev;
- tshem tawm cov kab mob tsis zoo thiab " qub";
- tiv thaiv kev txhim kho ntawm cov kab mob necrosis;
- hloov cov ntaub so ntswg thiab kabmob thaum lub sijhawm embryogenesis thiab ontogenesis;
- tshem tawm cov khoom tsis tsim nyog uas tau ua tiav lawv txoj haujlwm;
- tshem tawm cov hlwb uas tsis xav tau lossis txaus ntshai rau lub cev (mutant, qog, kis tus kabmob);
- kev tiv thaiv kab mob.
Yog li, apoptosis yog ib txoj hauv kev los tswj cov cell-tissue homeostasis.
Nyob hauv cov nroj tsuagapoptosis feem ntau tshwm sim los thaiv kev sib kis ntawm cov ntaub so ntswg kis kab mob parasitic agrobacteria.
Stages of cell death
Dab tsi tshwm sim rau lub xov tooj ntawm tes thaum lub sijhawm apoptosis yog qhov tshwm sim ntawm cov kab sib txuas ntawm cov molecular kev sib cuam tshuam ntawm cov enzymes sib txawv. Kev tshwm sim tshwm sim raws li qhov cascade, thaum qee cov proteins qhib rau lwm tus, pab txhawb kev loj hlob zuj zus ntawm qhov xwm txheej tuag. Cov txheej txheem no tuaj yeem muab faib ua ob peb theem:
- Induction.
- Ua kom cov proteins proapoptotic.
- Kev ua haujlwm ntawm caspase.
- Kev rhuav tshem thiab rov tsim kho cov kab mob ntawm tes.
- Kev tsim ntawm apoptocytes.
- Kev npaj ntawm cov khoom tawg ntawm tes rau phagocytosis.
Qhov kev sib txuas ntawm tag nrho cov khoom tsim nyog los tso tawm, siv thiab tswj txhua theem yog cov caj ces, uas yog vim li cas apoptosis hu ua programmed cell tuag. Kev ua kom cov txheej txheem no yog nyob rau hauv kev tswj hwm nruj ntawm cov txheej txheem tswj hwm, suav nrog ntau yam inhibitors ntawm CHG.
Molecular mechanisms ntawm cell apoptosis
Kev loj hlob ntawm apoptosis yog txiav txim los ntawm kev ua ke ntawm ob lub tshuab molecular: induction thiab effector. Thawj qhov thaiv yog lub luag haujlwm rau kev tswj hwm kev tso tawm ntawm ZGK. Nws suav nrog lub npe hu ua tuag receptors, Cys-Asp-proteases (caspases), ib tug xov tooj ntawm mitochondrial Cheebtsam, thiab pro-apoptotic proteins. Tag nrho cov ntsiab lus ntawm qhov induction theem tuaj yeem muab faib ua qhov tshwm sim (sib koom hauv induction) thiab cov modulators uas muab kev hloov pauv ntawm cov teeb liab tuag.
Cov txheej txheem effector muaj cov cuab yeej molecular uas ua kom cov degradation thiab restructuring ntawm cellular Cheebtsam. Kev hloov pauv ntawm theem thawj thiab theem thib ob tshwm sim nyob rau theem ntawm proteolytic caspase cascade. Nws yog vim yog cov khoom ntawm effector thaiv uas cell tuag tshwm sim thaum apoptosis.
Apoptosis factor
Cov qauv-morphological thiab biochemical hloov pauv thaum lub sijhawm apoptosis yog ua los ntawm qee yam ntawm cov cuab yeej tshwj xeeb ntawm tes, cov tseem ceeb tshaj plaws yog caspases, nucleases thiab membrane modifiers.
Caspases yog ib pawg ntawm cov enzymes uas txiav peptide bonds ntawm asparagine residues, fragmenting proteins rau hauv loj peptides. Ua ntej pib ntawm apoptosis, lawv muaj nyob rau hauv lub cell nyob rau hauv ib tug inactive lub xeev vim inhibitors. Lub hom phiaj tseem ceeb ntawm caspases yog nuclear proteins.
Nucleases yog lub luag haujlwm rau txiav DNA molecules. Tshwj xeeb tshaj yog tseem ceeb nyob rau hauv txoj kev loj hlob ntawm apoptosis yog lub active endonuclease CAD, uas lov chromatin cheeb tsam nyob rau hauv cov cheeb tsam ntawm linker sequences. Yog li ntawd, cov khoom tawg nrog qhov ntev ntawm 120-180 nucleotide khub yog tsim. Cov nyhuv nyuaj ntawm proteolytic caspases thiab nucleases ua rau deformation thiab fragmentation ntawm nucleus.
Cell membrane modifiers - rhuav lub asymmetry ntawm bilipid txheej, tig mus rau hauv lub hom phiaj rau phagocytic hlwb.
Lub luag haujlwm tseem ceeb hauv kev txhim kho ntawm apoptosis belongs rau caspases, uas maj mam qhib tag nrho cov txheej txheem tom ntej ntawm degradation thiab morphological rearrangement.
Lub luag haujlwm ntawm caspase hauv cellulartuag
Tsev neeg caspase suav nrog 14 cov proteins. Qee tus ntawm lawv tsis koom nrog apoptosis, thaum lwm tus tau muab faib ua 2 pawg: pib (2, 8, 9, 10, 12) thiab effector (3, 6, thiab 7), uas yog hu ua thib ob-tier caspases. Tag nrho cov proteins no yog synthesized li precursors - procaspases, qhib los ntawm proteolytic cleavage, lub essence ntawm uas yog lub detachment ntawm lub N-terminal domain thiab faib ntawm cov seem molecule rau hauv ob qhov chaw, tom qab ntawd txuam rau hauv dimers thiab tetramers.
Initiator caspases yuav tsum tau qhib ib pawg effector uas nthuav tawm cov haujlwm proteolytic tawm tsam ntau yam tseem ceeb ntawm cov cellular proteins. Ob-theem caspase substrates suav nrog:
- kho DNA enzymes;
- p-53 protein inhibitor;
- poly-(ADP-ribose)-polymerase;
- inhibitor ntawm DNase DFF (kev puas tsuaj ntawm cov protein no ua rau ua rau CAD endonuclease), thiab lwm yam.
Tag nrho cov hom phiaj rau cov nyhuv caspases yog ntau dua 60 cov proteins.
Kev txwv tsis pub ntawm cell apoptosis tseem ua tau nyob rau theem ntawm kev ua kom cov neeg pib procaspases. Thaum effector caspases tau qhib, cov txheej txheem yuav hloov tsis tau.
Apoptosis activation pathways
Kev xa tawm mus rau pib cell apoptosis tuaj yeem ua tau ob txoj hauv kev: receptor (lossis sab nraud) thiab mitochondrial. Hauv thawj kis, cov txheej txheem tau qhib los ntawm cov neeg tuag tshwj xeeb uas pom cov cim sab nraud, uas yog cov proteins ntawm TNF (cov qog necrosis factor) tsev neeg lossis Fas ligands nyob rau saum npoo. T-killers.
Tus receptor suav nrog 2 lub luag haujlwm ua haujlwm: ib qho transmembrane (tsim los khi rau ligand) thiab "tus neeg tuag" taw rau hauv lub cell, uas ua rau apoptosis. Cov txheej txheem ntawm txoj kev receptor yog raws li kev tsim ntawm DISC complex uas ua rau cov neeg pib caspases 8 lossis 10.
Lub rooj sibtham pib nrog kev sib cuam tshuam ntawm qhov chaw tuag nrog cov proteins hauv cov cellular adapter, uas nyob rau hauv lem khi pib procaspases. Raws li ib feem ntawm txoj kev, cov tom kawg tau hloov mus rau hauv kev ua haujlwm ua haujlwm caspases thiab ua rau muaj qhov apoptotic cascade ntxiv.
Lub txheej txheem ntawm txoj hauv kev sab hauv yog ua raws li kev ua kom cov proteolytic cascade los ntawm cov mitochondrial proteins tshwj xeeb, tso tawm uas yog tswj los ntawm intracellular signals. Kev tso tawm ntawm cov khoom organelle yog ua los ntawm kev tsim cov pores loj.
Cytochrome c ua lub luag haujlwm tshwj xeeb hauv kev tshaj tawm. Ib zaug nyob rau hauv cytoplasm, cov khoom no ntawm cov saw hlau electrotransport khi rau Apaf1 protein (ib qho apoptotic protease activating factor), uas ua rau kev ua kom lub tom kawg. Apaf1 tom qab ntawd raug khi los ntawm tus pib procaspases 9, uas ua rau apoptosis los ntawm kev ua haujlwm cascade.
Kev tswj txoj hauv kev sab hauv yog ua los ntawm ib pab pawg tshwj xeeb ntawm cov proteins ntawm tsev neeg Bcl12, uas tswj kev tso tawm ntawm cov khoom nruab nrab ntawm mitochondria rau hauv cytoplasm. Tsev neeg muaj ob qho tib si pro-apoptotic thiab anti-apoptotic proteins, qhov sib npaug ntawm qhov kev txiav txim seb tus txheej txheem yuav pib.
Ib yam muaj zog uas ua rau apoptosis los ntawm mitochondrial mechanism yog reactivecov ntaub ntawv ntawm oxygen. Lwm qhov tseem ceeb inducer yog p53 protein, uas ua rau txoj kev mitochondrial nyob rau hauv lub xub ntiag ntawm DNA puas.
Qee lub sij hawm pib ntawm cell apoptosis ua ke ob txoj hauv kev ib zaug: ob qho tib si sab nraud thiab sab hauv. Cov tom kawg feem ntau ua haujlwm los txhim kho receptor activation.
