Los ntawm Cocer Peptides 
1 month ago
Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.
Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.
Txheej txheem cej luam
Cellular aging yog ib qho tseem ceeb ntawm cov txheej txheem lom nyob rau hauv cov kab mob nyob thiab yog ze ze rau ntau yam physiological thiab pathological phenomena. Raws li lub hnub nyoog nce, cellular aging maj mam accumulates, ua rau poob ntawm cov ntaub so ntswg thiab lub cev ua haujlwm thiab ua rau ntau yam kab mob uas muaj hnub nyoog. Peptides, raws li chav kawm ntawm bioactive molecules tseem ceeb, tau txais kev saib xyuas tseem ceeb hauv kev tshawb fawb ntawm cellular aging nyob rau xyoo tas los no. Kev tshawb fawb qhia tias peptides ua lub luag haujlwm tseem ceeb hauv kev tswj cov txheej txheem kev laus ntawm tes. Tshawb nrhiav kev sib raug zoo ntawm peptides thiab cellular aging yog qhov tseem ceeb heev rau elucidating cov txheej txheem ntawm kev laus thiab txhim kho kev tiv thaiv kev laus.
Daim duab 1. Mechanisms ntawm daim tawv nqaij laus txheej txheem. (a) Dawb radicals thiab oxidative kev nyuaj siab txoj kev xav. Mitochondria tsim ROS los ntawm oxidative metabolism. ROS ntau dhau tuaj yeem ua rau cov kab mob mitochondrial thiab DNA, ua rau txo qis hauv cov qib collagen thiab nce qib MMP hauv cov ntaub so ntswg. ( b ) Inflamation theory. Senescent fibroblasts thiab keratinocytes secrete ntau ntawm senescence-associated secretory phenotypes, xws li TNF-α, IL-1, IL-6, IFN-γ thiab MMPs. Cov cytokines proinflammatory no ua rau cov tawv nqaij ntawm cov cell senescence los ntawm kev txhawb ROS ntau lawm thiab ua kom lub ATM / p53 / p21-cim txoj hauv kev. ( c ) Photoaging theory. Ultraviolet irradiation induces zus tau tej cov ROS thiab tso tawm ntawm MMPs, uas degrades daim tawv nqaij extracellular matrix Cheebtsam xws li collagen. ( d ) Nonenzymatic glycosyl chemistry txoj kev xav. Non-enzymatic glycosylation yog cov tshuaj tiv thaiv ntawm kev txo cov suab thaj dawb thiab dawb amino pawg ntawm cov proteins, DNA thiab lipids los tsim AGEs thiab ROS. Kev sib sau ntawm AGEs, ua ke nrog ROS, tuaj yeem ua rau muaj kev hloov pauv hauv cell homeostasis thiab cov qauv protein.
Cellular Aging
(1) Lub tswv yim thiab yam ntxwv ntawm Cellular Aging
Cellular aging yog hais txog qhov kev loj hlob tsis tuaj yeem raug ntes hauv lub xeev uas cov hlwb nkag mus tom qab muaj qee qhov kev faib lossis raug cuam tshuam rau cov kev ntxhov siab tshwj xeeb. Nws nthuav tawm cov yam ntxwv zoo ib yam, xws li kev hloov pauv hauv cell morphology, suav nrog kev ntim ntawm tes, flattening, thiab vacuolization ntawm cytoplasm; cell voj voog raug ntes, nrog cov hlwb tsis proliferating; thiab nce kev ua haujlwm ntawm senescence-associated β-galactosidase (SA-β-gal), uas yog tam sim no yog ib qho ntawm feem ntau siv cov cim ntawm cellular senescence. Hloov pauv secretory phenotype, qhov twg cov hlwb secrete ntau yam cytokines, chemokines, thiab proteases, tsim cov senescence-associated secretory phenotype (SASP).
(2) Qhov tshwm sim ntawm Cellular Senescence
Deterioration ntawm cov ntaub so ntswg thiab lub cev ua haujlwm
Cells yog lub hauv paus tsim cov ntaub so ntswg thiab cov kabmob, thiab cellular senescence ua rau cov nqaij mos thiab lub cev ua haujlwm tsis zoo. Nyob rau hauv cov ntaub so ntswg ntawm daim tawv nqaij, senescent fibroblasts txo cov synthesis ntawm collagen thiab elastic fibers, ua rau daim tawv nqaij poob elasticity, tsim wrinkles, thiab muaj peev xwm kho tsis tau. Nyob rau hauv cov hlab plawv system, senescent endothelial hlwb tuaj yeem ua rau cov phab ntsa ntawm cov hlab ntsha khov thiab txo elasticity, ua rau muaj kev pheej hmoo ntawm cov kab mob plawv. Hauv lub cev tiv thaiv kab mob, kev laus ntawm lub cev tiv thaiv kab mob ua rau lub cev tsis muaj zog tiv thaiv kev ua haujlwm, ua rau tib neeg muaj kev cuam tshuam rau cov kab mob cuam tshuam thiab txo lawv lub cev tiv thaiv kab mob rau cov tshuaj tiv thaiv.
Koom nrog cov kab mob uas muaj hnub nyoog
Cell aging yog suav hais tias yog ib qho tseem ceeb ntawm kev tsav tsheb hauv ntau yam kab mob uas muaj hnub nyoog. Hauv cov kab mob neurodegenerative xws li Alzheimer's disease thiab Parkinson's disease, neuronal aging yog ze rau cov txheej txheem pathological xws li neuronal tuag thiab neuroinflamation. Hauv kev mob ntshav qab zib mellitus, kev laus ntawm pancreatic β hlwb tuaj yeem ua rau cov tshuaj insulin tsis txaus, cuam tshuam rau cov ntshav qabzib cov cai. Cell senescence kuj muaj kev sib raug zoo nrog tumorigenesis thiab qog kev loj hlob. Thaum ntxov cell senescence tuaj yeem ua raws li cov qog nqaij hlav, tiv thaiv qhov kev loj hlob tsis kawg ntawm cov hlwb puas. Txawm li cas los xij, nyob rau hauv cov qog microenvironment, SASP Cheebtsam secreted los ntawm senescent hlwb yuav txhawb cov qog cell loj hlob, ntxeem tau, thiab metastasis.
Peptides
(1) Txhais thiab qauv ntawm peptides
Peptides yog cov sib txuas luv luv uas tsim los ntawm cov amino acids txuas ntawm peptide bonds. Raws li tus naj npawb ntawm cov amino acid residues lawv muaj, lawv tuaj yeem muab faib ua dipeptides, tripeptides, tetrapeptides, thiab polypeptides, thiab lwm yam. Polypeptides ntev dua, txuas ntxiv, thiab tsis muaj kab peptide chains. Feem ntau, peptide chains uas tsis muaj ntau tshaj 50 amino acids yog cais raws li peptides kom paub qhov txawv ntawm cov proteins. Txhua peptide chains, tshwj tsis yog rau cyclic peptides, muaj N-terminal (amino-terminal) thiab C-terminal (carboxy-terminal) residue.
(2) Kev faib tawm ntawm Peptides
Classification los ntawm Source
Endogenous peptides: synthesized los ntawm kab mob nws tus kheej thiab ua ntau yam physiological functions nyob rau hauv lub cev. Neuropeptides, uas koom nrog hauv cov teeb liab kis tau tus mob thiab kev tswj hwm nyob rau hauv lub paj hlwb, nrog rau endorphins thiab enkephalins, uas muaj analgesic thiab mus ob peb vas-regulating teebmeem; hormone peptides, xws li insulin, uas yog qhov tseem ceeb rau kev tswj cov ntshav qab zib kom tsawg.
Exogenous peptides: tau los ntawm cov khoom noj lossis lwm qhov chaw sab nraud. Piv txwv li, qee cov zaub mov muaj protein ntau tuaj yeem hydrolyzed los ntawm digestive enzymes los tsim bioactive peptides, xws li mis nyuj peptides, uas muaj ntau yam physiological functions, xws li antioxidant thiab tiv thaiv kab mob. Peptides npaj los ntawm cov tshuaj synthesis lossis biotechnology kuj poob rau hauv exogenous peptides thiab feem ntau siv rau hauv kev tsim tshuaj thiab kev kho mob.
Classification los ntawm Function
Antioxidant Peptides: Muaj peev xwm tshem tawm cov dawb radicals hauv lub cev thiab txo cov oxidative kev nyuaj siab vim kev puas tsuaj rau cov hlwb. Piv txwv li, nplej bran antioxidant peptides tau pom tias yuav txhim kho cov kev ua ntawm antioxidant enzymes xws li catalase (CAT) thiab glutathione peroxidase (GSH-Px) nyob rau hauv mitochondria ntawm lub plawv thiab lub hlwb cov ntaub so ntswg ntawm D-galactose-induced aged nas, txo cov theem ntawm mitochondrial DNA deletion mutations nyob rau hauv lub hlwb.
Immune-modulating peptides: Cov no tswj lub cev tiv thaiv kab mob ua haujlwm, txhim kho lossis tiv thaiv kev tiv thaiv kab mob. Qee cov peptides muab tau los ntawm cov kab mob hauv hiav txwv tuaj yeem ua rau lub cev tiv thaiv kab mob, txhim kho lub cev tiv thaiv kab mob, thiab pab tiv thaiv kab mob thiab qog nqaij hlav.
Cell loj hlob-regulating peptides: Cov no cuam tshuam cov txheej txheem ntawm tes xws li kev loj hlob, kev sib txawv, thiab apoptosis. Piv txwv li, epidermal growth factor (EGF) txhawb kev loj hlob thiab kev sib txawv ntawm cov kab mob epidermal, ua kom lub qhov txhab zoo.
Lub luag haujlwm ntawm peptides hauv cellular aging
(1) Kev tswj ntawm mitochondrial muaj nuj nqi
Mitochondria ua lub luag haujlwm tseem ceeb hauv kev tsim hluav taws xob ntawm tes thiab cov teeb liab hloov pauv, thiab lawv txoj haujlwm tsis zoo yog cuam tshuam nrog kev laus ntawm tes. Mitochondria-derived peptides (MDPs) xws li humanin thiab MOTS-c ua si lub luag haujlwm tseem ceeb hauv kev laus ntawm tes. Tom qab kev qaug dab peg tshwm sim los ntawm kev qaug zog, doxorubicin, lossis kev kho hydrogen peroxide hauv thawj tib neeg fibroblasts, mitochondrial tus lej nce, mitochondrial ua pa theem nce, thiab humanin thiab MOTS-c qib kuj nce. Kev tswj hwm ntawm humanin thiab MOTS-c me ntsis nce mitochondrial respiration nyob rau hauv doxorubicin-induced senescent hlwb thiab ib feem tswj SASP Cheebtsam ntawm JAK txoj kev, qhia tias MDPs ua lub luag haujlwm tseem ceeb hauv mitochondrial zog metabolism thiab SASP ntau lawm hauv senescent hlwb.
Daim duab 2 Mitochondrial loj thiab lub zog tau hloov pauv thaum doxorubicin-induced senescence. (A) Mitochondrial DNA (mtDNA) luam tus lej nyob rau hauv non-senescent (quiescent) thiab senescent hlwb. (B) Cov duab sawv cev ntawm Tom20 (ntsuab; mitochondria) thiab Hoechst 33258 (xiav; nucleus) immunostaining hauv non-senescent (quiescent) thiab senescent hlwb. Scale bar, 20 μm. Thaj tsam ntawm Tom20 staining ib lub xov tooj tau ntsuas siv ImageJ. (C) Cellular ATP theem nyob rau hauv non-senescent (quiescent) thiab senescent hlwb. (D) Cellular oxygen noj tus nqi (OCR) nyob rau hauv non-senescent thiab senescent hlwb. Kev ua pa basal, lub peev xwm ua pa seem, thiab ATP ntau lawm yog xam raws li kev txhaj tshuaj raws li cov chaw tsim khoom cov lus qhia. (E) Lub extracellular acidification tus nqi (ECAR) nyob rau hauv non-senescent (quiescent) thiab senescent hlwb.
(2) Kev cuam tshuam rau kev laus-txog kev taw qhia txoj hauv kev
p53p21 ua
P53 protein yog ib qho tseem ceeb regulator ntawm cellular senescence. Thaum cov hlwb raug cuam tshuam rau cov kev ntxhov siab xws li DNA puas, p53 yog qhib, inducing cov kev qhia ntawm p21, uas ua rau lub cell mus ntes nyob rau theem G1, ua rau cellular senescence. Qee cov peptides tuaj yeem hloov kho txoj hauv kev p53-p21, yog li cuam tshuam qhov kev loj hlob ntawm cellular senescence. Qee qhov me me-molecule peptides tuaj yeem cuam tshuam nrog p53 protein, inhibiting nws cov haujlwm thiab ua rau qeeb cellular senescence. Cov kev tshawb fawb tau pom tias cov peptides tshwj xeeb tuaj yeem thaiv kev sib cuam tshuam ntawm p53 thiab MDM2 (cov protein uas tsis zoo tswj p53), ua kom cov p53 protein nyob ruaj khov thiab tswj nws ntawm qhov tsim nyog kom tsis txhob muaj kev ua kom ntau dhau ua rau cellular senescence.
Rb-E2F txoj kev
Rb protein yog lwm qhov tseem ceeb ntawm cov kab ke tswj hwm cov protein uas khi rau E2F kev hloov pauv mus rau inhibit qhov kev qhia ntawm lub voj voog ntawm cov noob caj noob ces. Thaum Rb protein yog phosphorylated thiab inactivated, E2F raug tso tawm, txhawb cell nkag mus rau theem S rau DNA replication. Thaum lub sijhawm cellular senescence, kev hloov pauv hauv Rb-E2F txoj hauv kev ua rau lub voj voog ntawm tes raug ntes. Qee cov peptides tuaj yeem tswj hwm cellular senescence los ntawm kev hloov kho lub xeev phosphorylation ntawm Rb protein lossis cuam tshuam E2F kev ua haujlwm. Qee cov peptides tuaj yeem cuam tshuam Rb protein phosphorylation, tswj kev ruaj ntseg ntawm Rb-E2F complex thiab yog li ncua cellular senescence.
(III) Regulation of SASP
SASP suav nrog ntau yam cytokines, chemokines, thiab proteases, thiab lwm yam. Nws secretion tsis tsuas yog cuam tshuam rau microenvironment ntawm cov hlwb senescent lawv tus kheej tab sis kuj cuam tshuam cov ntaub so ntswg thiab cov hlwb, txhawb kev inflammatory teb thiab cov ntaub so ntswg senescence. Qee cov peptides tuaj yeem tswj hwm SASP ntau lawm thiab txo nws cov teebmeem. Qee cov nroj tsuag-derived peptides kuj tau pom los tswj SASP los ntawm inhibiting kev ua kom cov kev taw qhia tshwj xeeb thiab txo cov kev qhia ntawm SASP ntsig txog yam.
Daim ntawv thov ntawm Peptides hauv Kev Ncua Cellular Aging
(1) Kev siv hauv cov khoom siv tawv nqaij
Nrog rau pej xeem kev txhawj xeeb txog kev laus ntawm daim tawv nqaij, peptides tau pom muaj ntau daim ntawv thov hauv kev lag luam tu tawv nqaij. Piv txwv li, qee cov khoom siv tawv nqaij uas muaj peptides thov kom muaj kev tiv thaiv kev ua kom tawv nqaij thiab tawv nqaij. Kev tshawb fawb qhia tias qee yam peptides tuaj yeem txhawb nqa collagen synthesis thiab txhim kho daim tawv nqaij elasticity. Peptides tseem tuaj yeem tswj hwm cov cell cell metabolism, txhim kho daim tawv nqaij ua haujlwm tsis zoo, txo kev puas tsuaj rau cov hlwb los ntawm lwm yam xws li UV hluav taws xob, thiab ua rau cov tawv nqaij laus zuj zus.
Daim duab 3 Kev laus ntawm daim tawv nqaij hluas rau cov laus.
(2) Cov ntawv thov hauv Kev Txhim Kho Tshuaj
Kev Kho Cov Kab Mob Neurodegenerative
Peptide tshuaj txhim kho tuav cov lus cog tseg zoo rau kev hais txog kev laus hauv cov kab mob neurodegenerative. Peptides uas tswj cov kev taw qhia intracellular, txhawb kev muaj sia nyob neuronal, thiab pab kho kho tau tsim los kho Alzheimer's kab mob thiab Parkinson's disease. Qee cov peptides tuaj yeem tiv thaiv kev sib sau ntawm cov proteins tsis zoo hauv cov neurons, txo cov kab mob neuroinflammation, thiab ncua kev laus thiab kev tuag. Lub peptide hu ua AC-5216 tuaj yeem cuam tshuam kev sib sau ntawm β-amyloid proteins thiab txhim kho kev txawj ntse hauv Alzheimer tus kab mob qauv nas.
Kev kho mob plawv
Hauv kev kho cov kab mob plawv, cov tshuaj peptide tuaj yeem tsom cov txheej txheem pathological xws li vascular endothelial cell aging thiab myocardial cell aging. Piv txwv li, qee qhov vasoactive peptides tuaj yeem tswj hwm vascular tone thiab endothelial cell muaj nuj nqi, txhim kho kev laus ntawm vascular endothelial hlwb, thiab txo cov kev pheej hmoo ntawm cov kab mob plawv. Qee cov peptides tuaj yeem txhawb kev kho thiab rov tsim dua tshiab ntawm cov hlwb myocardial, muab cov ntawv thov hauv kev kho mob xws li myocardial infarction.
Xaus
Cell aging, raws li ib tug complex biological txheej txheem, influences kev noj qab haus huv thiab aging txheej txheem ntawm lub cev. Peptides, raws li chav kawm tseem ceeb ntawm bioactive molecules, ua si ntau lub luag haujlwm hauv kev tswj cov cell laus. Los ntawm kev tswj hwm mitochondrial muaj nuj nqi, cuam tshuam hauv kev laus-txog kev teeb tsa txoj hauv kev, thiab hloov kho SASP, peptides qhia lub peev xwm los ncua kev laus ntawm tes.
Qhov chaw
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