By Cocer Peptides 
1 ọnwa gara aga
Edemede na ozi ngwaahịa niile enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.
Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadoghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.
Nchịkọta
Ịka nká nke cell bụ usoro dị mkpa dị ndụ n'ime ihe ndị dị ndụ ma nwee njikọ chiri anya na ọtụtụ ihe omume physiological na pathological. Ka afọ na-abawanye, cellular ịka nká na-eji nwayọọ nwayọọ na-agbakọta, na-eduga n'ịdalata nke anụ ahụ na ọrụ akụkụ ahụ ma na-ebute ọrịa dị iche iche metụtara afọ. Peptides, dị ka otu klas nke ụmụ irighiri ihe dị mkpa nke bioactive, enwetala nlebara anya dị ukwuu na ngalaba nyocha ịka nká nke ekwentị n'afọ ndị na-adịbeghị anya. Nnyocha na-egosi na peptides na-ekere òkè dị mkpa n'ịhazi usoro ịka nká nke cellular. Ịchọgharị mmekọrịta dị n'etiti peptides na ịka nká cellular bụ ihe dị mkpa maka ịkọwapụta usoro nke ịka nká na ịmepụta ihe mgbochi ịka nká.
Ọgụgụ 1. Usoro nke usoro ịka nká akpụkpọ anụ. (a) Free radicals na oxidative stress theory. Mitochondria na-emepụta ROS site na metabolism oxidative. Oke ROS nwere ike imebi akụkụ mitochondrial na DNA, na-eduga mbelata ọkwa collagen na mmụba nke ọkwa MMP na anụ ahụ anụ ahụ. ( b ) Ozizi mbufụt. Senescent fibroblasts na keratinocytes na-ezobe ọnụ ọgụgụ dị ukwuu nke senescence metụtara nzuzo nzuzo phenotypes, gụnyere TNF-α, IL-1, IL-6, IFN-γ na MMPs. Cytokines ndị a na-akpali akpali na-ebute senescence cell anụ ahụ site n'ịkwalite mmepụta ROS na ịgbalite ụzọ akara ATM/p53/p21. ( c ) Ozizi foto. Ultraviolet irradiation na-akpali mmepụta nke ROS na nzuzo nke MMPs, nke na-eweda akpụkpọ anụ extracellular matrix components dị ka collagen. ( d ) Theory chemistry Nonenzymatic glycosyl. Glycosylation na-abụghị enzymatic bụ mmeghachi omume n'etiti mbelata shuga n'efu na otu amino dị iche iche nke protein, DNA na lipids iji mepụta AGE na ROS. Nchịkọta AGEs, yana ROS, nwere ike iduga mgbanwe na cell homeostasis na protein nhazi.
Cellular ịka nká
(1) Echiche na njirimara nke ịka nká nke cellular
Ịka nká nke cellular na-ezo aka na njide uto na-apụghị ịgbagha agbagha nke mkpụrụ ndụ na-abanye ma ọ bụrụ na ha nwesịrị ọnụ ọgụgụ nke nkewa ma ọ bụ na-ekpughere ya na ihe mgbagwoju anya. Ọ na-egosiputa usoro nke njirimara, dị ka mgbanwe nke mkpụrụ ndụ mkpụrụ ndụ, gụnyere ụbara ụda cell, ịha nhata, na nkwụsị nke cytoplasm; njide okirikiri cell, na mkpụrụ ndụ anaghịzi amụba; na mmụba ọrụ nke senescence-metụtara β-galactosidase (SA-β-gal), nke bụ ugbu a otu n'ime ihe nrịbama nke cellular senescence. phenotype nzuzo gbanwere, ebe mkpụrụ ndụ na-ezobe cytokines dị iche iche, chemokines, na proteases, na-eme ka senescence-metụtara secretory phenotype (SASP).
(2) Nsonaazụ nke Senescence Cellular
Mbelata nke anụ ahụ na ọrụ akụkụ ahụ
Selụ bụ ihe ndị bụ isi na-ewu anụ ahụ na akụkụ ahụ, na senescence cell na-eduga n'ịrụ ọrụ anụ ahụ na akụkụ ahụ. N'ime anụ ahụ anụ ahụ, fibroblasts senescent na-ebelata njikọ nke collagen na eriri na-agbanwe agbanwe, na-eme ka akpụkpọ ahụ ghara ịdị nro, na-etolite wrinkles, na enwekwaghị ikike nrụzi. N'ime usoro obi obi, mkpụrụ ndụ endothelial senescent nwere ike iduga mgbidi arịa ọbara na-agbaze ma belata ngbanwe, na-abawanye ohere nke ọrịa obi. N'ime usoro ahụ ji alụso ọrịa ọgụ, ịka nká nke mkpụrụ ndụ na-alụso ọrịa ọgụ na-ebelata ọrụ nchebe nke ahụ, na-eme ka ndị mmadụ nwee ike ịbanye na mbuso agha pathogen na ibelata nzaghachi mgbochi ha na ọgwụ mgbochi.
Njikọ na ọrịa ndị metụtara afọ
A na-ahụta ịka nká cell dị ka ihe dị mkpa na-anya ụgbọ ala n'ọtụtụ ọrịa ndị metụtara afọ. Na ọrịa neurodegenerative dị ka ọrịa Alzheimer na ọrịa Parkinson, neuronal ịka nká na-ejikọta ya na usoro pathological dị ka ọnwụ neuronal na neuroinflammation. N'ime ọrịa shuga mellitus, ịka nká nke mkpụrụ ndụ beta pancreatic nwere ike ibute ụkọ insulin zuru oke, na-emetụta ụkpụrụ glucose ọbara nkịtị. Senescence cell nwekwara mmekọrịta dị mgbagwoju anya na tumorigenesis na ọganihu etuto ahụ. Senescence nke mbụ nwere ike ịrụ ọrụ dị ka usoro nkwụsị nke tumor, na-egbochi mmụba na-enweghị njedebe nke mkpụrụ ndụ mebiri emebi. Otú ọ dị, na microenvironment tumor, akụkụ SASP zoro ezo site na mkpụrụ ndụ senescent nwere ike ịkwalite uto cell tumor, mbuso agha, na metastasis.
Peptides
(1) Nkọwa na nhazi nke peptides
Peptides bụ ogige mkpirisi yinye nke amino acid jikọtara site na njikọ peptide. Dabere na ọnụọgụ amino acid dị n'ime ha, enwere ike kewaa ha n'ime dipeptides, tripeptides, tetrapeptides, na polypeptides, n'etiti ndị ọzọ. Polypeptides dị ogologo, na-aga n'ihu, na agbụ peptide enweghị alaka. Dịka, agbụ peptide enweghị ihe karịrị amino acid 50 ka a na-ekewa dị ka peptides iji mata ọdịiche dị na protein. Agbụ peptide niile, ewezuga peptides cyclic, nwere N-terminal (amino-terminal) na ihe fọdụrụ C-terminal (carboxy-terminal).
(2) Nhazi nke Peptides
Nhazi site na Isi mmalite
Endogenous peptides: synthesized site organism n'onwe ya na-arụ ọrụ dị iche iche physiological n'ime ahụ. Neuropeptides, nke na-ekere òkè na nnyefe mgbaàmà na nhazi n'ime usoro ụjọ ahụ, gụnyere endorphins na enkephalins, nke nwere mmetụta analgesic na mmetụta na-achịkwa ọnọdụ; peptides hormone, dị ka insulin, nke dị mkpa maka ịhazi nguzozi nke shuga n'ọbara.
Exogenous peptides: enwetara site na nri ma ọ bụ isi mmalite ndị ọzọ. Dịka ọmụmaatụ, ụfọdụ protein nri nwere ike ịmegharị ya site na enzymes digestive iji mepụta peptides bioactive, dị ka peptides mmiri ara ehi, nke nwere ọtụtụ ọrụ physiological, gụnyere antioxidant na mgbochi-modulating mmetụta. Peptides akwadoro site na njikọ kemịkalụ ma ọ bụ nkà na ụzụ biotechnology na-adaba n'okpuru peptides exogenous ma na-ejikarị na mmepe ọgwụ na ọgwụgwọ ụlọ ọgwụ.
Nkewa site na Ọrụ
Peptides Antioxidant: Nwere ike ihichapụ radicals n'efu na ahụ yana ibelata nrụgide oxidative kpatara mmebi nke mkpụrụ ndụ. Dịka ọmụmaatụ, egosila peptides antioxidant osikapa bran iji welie ọrụ nke enzymes antioxidant dị ka catalase (CAT) na glutathione peroxidase (GSH-Px) na mitochondria nke obi na ụbụrụ ụbụrụ nke ụmụ oke D-galactose kpatara agadi, na-ebelata ọkwa nke mitochondrial DNA na-ehichapụ mutations na ụbụrụ.
peptides na-eme ka mgbochi ọrịa: Ndị a na-achịkwa ọrụ mgbochi nke anụ ahụ, na-akwalite ma ọ bụ na-egbochi nzaghachi mgbochi. Ụfọdụ peptides sitere na ihe ndị dị n'ime mmiri nwere ike ime ka mkpụrụ ndụ na-alụso ọrịa ọgụ rụọ ọrụ, kwalite ikike nchebe nke ahụ, ma nyere aka n'iguzogide ọrịa nje na mmepe tumor.
peptides na-achịkwa uto cell: Ndị a na-emetụta usoro cellular dị ka mmụba, ọdịiche, na apoptosis. Dịka ọmụmaatụ, ihe na-eto eto na-eto eto (EGF) na-akwalite mmụba na ọdịiche nke mkpụrụ ndụ epidermal, na-eme ka ọnya na-agwọ ọrịa ngwa ngwa.
Ọrụ nke peptides na ịka nká cellular
(1) Iwu nke ọrụ mitochondrial
Mitochondria na-ekere òkè dị mkpa na mmepụta ume cell na ntụgharị mgbaàmà, na arụrụ ọrụ ha nwere njikọ chiri anya na ịka nká cellular. Mitochondria-derived peptides (MDPs) dị ka humanin na MOTS-c na-arụ ọrụ nchịkwa dị mkpa na usoro ịka nká cellular. N'ịgbaso senescence kpatara site na ike ọgwụgwụ mmegharị, doxorubicin, ma ọ bụ hydrogen peroxide ọgwụgwọ na fibroblasts mmadụ bụ isi, ọnụọgụ mitochondrial na-abawanye, ọkwa iku ume mitochondrial na-ebili, na ọkwa humanin na MOTS-c na-ebulikwa elu. Nlekọta nke humanin na MOTS-c na-abawanye ume iku ume mitochondrial na mkpụrụ ndụ senescent doxorubicin ma na-achịkwa akụkụ SASP site na ụzọ JAK, na-egosi na MDP na-arụ ọrụ dị mkpa na mitochondrial ume metabolism na SASP mmepụta na mkpụrụ ndụ senescent.
Ọnụ ọgụgụ 2 Mitochondrial mass na energetics na-agbanwe n'oge senescence nke doxorubicin kpatara. (A) Mitochondrial DNA (mtDNA) nọmba nnomi n'ime sel ndị na-abụghị senescent (quiescent) na mkpụrụ ndụ senescent. (B) Foto ndị nnọchianya nke Tom20 (green; mitochondria) na Hoechst 33258 (acha anụnụ anụnụ; nucleus) immunostaining na ndị na-abụghị senescent (quiescent) na senescent cell. Ogwe ọnụ ọgụgụ, 20 μm. A tụrụ mpaghara ntụpọ Tom20 kwa cell site na iji ImageJ. (C) Ọkwa ATP cellular na sel ndị na-abụghị senescent (quiescent) na sel senescent. (D) Ọnụego oriri oxygen cellular (OCR) n'ime sel ndị na-abụghị nke anụ ahụ na nke anụ ahụ. A na-agbakọ iku ume basal, ikike iku ume, yana mmepụta ATP dabere na ntinye ngwakọta usoro dịka ntuziaka onye nrụpụta siri dị. (E) Ọnụego acidification extracellular (ECAR) n'ime sel ndị na-abụghị senescent (quiescent) na sel senescent.
(2) Mmetụta na ụzọ mgbaàmà metụtara ịka nká
p53-p21 ụzọ
Protein p53 bụ isi ihe na-achịkwa senescence cell. Mgbe a na-ekpughere mkpụrụ ndụ ndị na-akpata nrụgide dị ka mmebi DNA, p53 na-arụ ọrụ, na-eme ka nkwupụta nke p21 pụta, nke na-eme ka ọkpụkpụ sel jide na oge G1, na-eduga na senescence cell. Ụfọdụ peptides nwere ike gbanwee ụzọ p53-p21, si otú ahụ na-emetụta ọganihu nke senescence cellular. Ụfọdụ peptides pere mpe nwere ike iso protein p53 na-emekọrịta ihe, na-egbochi ọrụ ya wee si otú a na-egbu oge senescence cellular. Nnyocha egosiwo na peptides pụrụ iche nwere ike igbochi mmekọrịta dị n'etiti p53 na MDM2 (protein nke na-achịkwa p53 na-adịghị mma), na-eme ka protein p53 guzosie ike ma na-edobe ya n'ogo kwesịrị ekwesị iji zere imebiga ihe ókè na-eduga na senescence cellular.
Rb-E2F ụzọ
Protein Rb bụ ihe ọzọ dị mkpa na-achịkwa usoro okirikiri cell nke na-ejikọta na ihe ederede E2F iji gbochie okwu nke mkpụrụ ndụ ihe nketa metụtara okirikiri. Mgbe protein Rb phosphorylated na arụghị ọrụ, E2F na-ahapụ ya, na-akwalite ntinye cell n'ime oge S maka ntụgharị DNA. N'oge senescence cellular, mgbanwe na ụzọ Rb-E2F na-eduga na njide okirikiri cell. Ụfọdụ peptides nwere ike ịhazi senescence cell site n'ịgbanwe ọnọdụ phosphorylation nke protein Rb ma ọ bụ na-emetụta ọrụ E2F. Ụfọdụ peptides nwere ike igbochi Rb protein phosphorylation, na-ejigide nkwụsi ike nke mgbagwoju Rb-E2F ma si otú a na-egbu oge senescence cellular.
(III) Iwu nke SASP
SASP nwere cytokines dị iche iche, chemokines, na proteases, n'etiti ndị ọzọ. Ihe nzuzo ya abụghị naanị na-emetụta microenvironment nke mkpụrụ ndụ senescent n'onwe ha kamakwa ọ na-emetụta anụ ahụ na sel ndị gbara ya gburugburu, na-akwalite nzaghachi mkpali na anụ ahụ anụ ahụ. Ụfọdụ peptides nwere ike ịhazi mmepụta SASP ma belata mmetụta ọjọọ ya. A chọpụtakwara na ụfọdụ peptides sitere na osisi na-achịkwa SASP site na igbochi mmalite nke ụzọ mgbaàmà kpọmkwem na ibelata okwu nke ihe ndị metụtara SASP.
Ngwa nke Peptides na igbu oge ịka nká
(1) Ngwa dị na ngwaahịa nlekọta anụ ahụ
Site na nchegbu ọha na eze na-arịwanye elu banyere ịka nká akpụkpọ ahụ, peptides achọtawo ngwa ngwa zuru oke na ụlọ ọrụ nlekọta anụ ahụ. Dịka ọmụmaatụ, ụfọdụ ngwaahịa nlekọta anụ ahụ nwere peptides na-ekwu na ha nwere mmetụta na-egbochi wrinkle na akpụkpọ ahụ. Nnyocha na-egosi na ụfọdụ peptides nwere ike ịkwalite njikọ nke collagen ma mee ka akpụkpọ ahụ dịkwuo mma. Peptides nwekwara ike ịhazi metabolism cell akpụkpọ ahụ, kwalite ọrụ mgbochi akpụkpọ ahụ, belata mmebi nke mkpụrụ ndụ akpụkpọ ahụ nke ihe ndị dị n'èzí dị ka UV radieshon kpatara, ma na-ebelata usoro ịka nká akpụkpọ ahụ.
Onyonyo 3 Ịka nká n'akpụkpọ ahụ nke nta ruo okenye.
(2) Ngwa na mmepe ọgwụ
Ọgwụgwọ nke Ọrịa Neurodegenerative
Mmepe ọgwụ peptide nwere nkwa dị ukwuu maka ibelata ịka nká neuronal na ọrịa neurodegenerative. Peptides nke na-achịkwa ụzọ mgbaàmà intracellular, na-akwalite nlanarị neuronal, na ịkwado nrụzi ka emepụtara maka ọgwụgwọ ọrịa Alzheimer na ọrịa Parkinson. Ụfọdụ peptides nwere ike igbochi nchịkọta nke protein ndị na-adịghị mma n'ime neurons, belata neuroinflammation, na igbu oge neuronal ịka nká na ọnwụ. Otu peptide aha ya bụ AC-5216 nwere ike igbochi nchịkọta nke protein β-amyloid ma melite ọrụ ọgụgụ isi na ụdị oke ọrịa Alzheimer.
Ọgwụgwọ ọrịa obi
Na ọgwụgwọ nke ọrịa obi, ọgwụ peptide nwere ike ikwado pathological usoro dị ka vaskụla endothelial cell ịka nká na myocardial cell ịka nká. Dịka ọmụmaatụ, ụfọdụ peptides vasoactive nwere ike ịhazi ụda vaskụla na ọrụ sel endothelial, melite ọnọdụ ịka nká nke mkpụrụ ndụ endothelial vaskụla, ma belata ihe ize ndụ nke ọrịa obi. Ụfọdụ peptides nwekwara ike ịkwalite nrụzi na mmeghari nke mkpụrụ ndụ myocardial, na-enye ngwa ndị nwere ike ịgwọ ọnọdụ dị ka infarction myocardial.
Mmechi
Ịka nká cell, dị ka usoro ihe omimi dị mgbagwoju anya, na-emetụta ahụike na usoro ịka nká nke ahụ. Peptides, dị ka klaasị dị mkpa nke ụmụ irighiri ihe na-eme ndụ ndụ, na-arụ ọrụ dị iche iche n'ịhazi ịka nká cell. Site n'ịchịkwa ọrụ mitochondrial, itinye aka na ụzọ mgbaàmà metụtara ịka nká, na imezi SASP, peptides na-egosipụta ikike igbu oge ịka nká cell.
Isi mmalite
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