Na Cocer Peptides 
ukwezi gushize
INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Z'UBUREZI.
Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.
Incamake
Gusaza kwa selile ninzira yingenzi yibinyabuzima mubinyabuzima kandi bifitanye isano rya bugufi nibintu byinshi bya physiologique na patologi. Uko imyaka igenda yiyongera, gusaza kwa selile bigenda byegeranya buhoro buhoro, biganisha ku kugabanuka kwimikorere yimikorere ningingo ndetse no gutera indwara zitandukanye ziterwa nimyaka. Peptide, nk'urwego rwa molekile zingenzi za bioaktique, zagiye zitaweho cyane mubijyanye n'ubushakashatsi bwo gusaza kwa selile mumyaka yashize. Ubushakashatsi bwerekana ko peptide igira uruhare runini mugutunganya ingirabuzimafatizo. Gucukumbura isano iri hagati ya peptide no gusaza kwa selile bifite akamaro kanini mugusobanura uburyo bwo gusaza no guteza imbere ingamba zo kurwanya gusaza.
Igishushanyo 1. Uburyo bwo gusaza uruhu. (a) radicals yubusa hamwe nigitekerezo cyo guhagarika umutima. Mitochondria itanga ROS ikoresheje metabolisme ya okiside. ROS ikabije irashobora kwangiza imiterere ya mitochondrial na ADN, bigatuma igabanuka rya kolagene ndetse no kwiyongera kwa MMP mubice byuruhu. ( b ) Igitekerezo cyo gutwika. Fibroblast ya Senescent na keratinocytes isohora umubare munini wa senescence ifitanye isano na senescence yibanga, harimo TNF-α, IL-1, IL-6, IFN-γ na MMPs. Iyi cytokine ya porinflammatory itera ingirabuzimafatizo y'uruhu mu guteza imbere umusaruro wa ROS no gukora inzira ya ATM / p53 / p21. ( c ) Igitekerezo cyo gufotora. Imirasire ya Ultraviolet itera umusaruro wa ROS hamwe no gusohora kwa MMPs, bitesha agaciro matrice idasanzwe ya materique nka kolagen. ( d ) Igitekerezo cya chimie ya nonczymatique glycosyl. Glycosylation idafite enzymatique ni reaction hagati yo kugabanya isukari yubusa hamwe nitsinda rya amino ryubusa rya poroteyine, ADN na lipide kugirango bibyare imyaka na ROS. Ikwirakwizwa rya AGEs, hamwe na ROS, birashobora gutuma habaho impinduka muri selile homeostasis hamwe na protein.
Gusaza kwa selile
(1) Igitekerezo n'ibiranga gusaza kwa selile
Gusaza kwa selile bivuga gufata bidasubirwaho gukura gufatwa ko selile zinjira nyuma yo gutandukana numubare runaka cyangwa guhura nibibazo byihariye. Irerekana urukurikirane rw'ibintu bisanzwe biranga, nk'impinduka muri morphologie selile, harimo kwiyongera k'utugingo ngengabuzima, gusibanganya, na vacuolisation ya cytoplazme; gufata ingirabuzimafatizo, hamwe na selile ntizongera kwiyongera; no kongera ibikorwa bya senescence ifitanye isano β-galactosidase (SA-β-gal), kuri ubu ikaba ari kimwe mu bimenyetso bikoreshwa cyane mu ngirabuzimafatizo. Guhindura ibanga rya fenotipike, aho selile zisohora cytokine zitandukanye, chemokine, na protease, bigakora senescence ifitanye isano na senotype yibanga (SASP).
(2) Ingaruka za Senescence ya Cellular
Kwangirika kw'imikorere n'imikorere y'ingingo
Ingirabuzimafatizo nizo shingiro zubaka zingirangingo ningingo, kandi senescence ya selile itera kwangirika kwimikorere nimikorere yumubiri. Mu ngingo z'uruhu, fibroblast ya senescent igabanya synthesis ya fibre ya kolagen na elastique, bigatuma uruhu rutakaza elastique, rukagira iminkanyari, kandi rukaba rwangiza ubushobozi bwo gusana. Muri sisitemu yumutima nimiyoboro y'amaraso, selile endothelial selile irashobora gutuma urukuta rw'imitsi ikomera kandi bikagabanya ubukana, bikongera ibyago byo kurwara umutima. Muri sisitemu yubudahangarwa, gusaza kwingirangingo z'umubiri bigabanya intege nke z'umubiri birinda umubiri, bigatuma abantu bakunze kwibasirwa na virusi kandi bikagabanya ubudahangarwa bwabo ku nkingo.
Ihuriro n'indwara ziterwa n'imyaka
Gusaza kwingirabuzimafatizo bifatwa nkimpamvu ikomeye itera indwara nyinshi ziterwa nimyaka. Mu ndwara zifata ubwonko nk'indwara ya Alzheimer n'indwara ya Parkinson, gusaza kwa neuronal bifitanye isano rya bugufi n'inzira z'indwara nk'urupfu rwa neuronal na neuroinflammation. Muri diyabete, gusaza kwa pancreatic β selile birashobora gutuma insuline idahagije, bigira ingaruka kumaraso asanzwe ya glucose. Senescence ya selile nayo ifitanye umubano utoroshye na tumorigenez no gutera ibibyimba. Senescence ya selile irashobora gukora nkuburyo bwo guhagarika ibibyimba, bikarinda ikwirakwizwa ryimipaka ingirabuzimafatizo zangiritse. Nyamara, muri microen ibidukikije yibibyimba, ibice bya SASP byasohowe na selile senescent birashobora gutuma imikurire yikibyimba ikura, gutera, na metastasis.
Peptide
(1) Ibisobanuro n'imiterere ya peptide
Peptide ni urunigi rugufi rwakozwe na aside amine ihujwe na peptide. Ukurikije umubare wibisigisigi bya aside amine birimo, birashobora gushyirwa mubice bya dipeptide, tripeptide, tetrapeptide, na polypeptide, nibindi. Polypeptide ni ndende, ikomeza, kandi idafite iminyururu ya peptide. Mubisanzwe, iminyururu ya peptide irimo aside amine itarenze 50 ishyirwa mubikorwa nka peptide kugirango ibatandukanye na poroteyine. Iminyururu ya peptide yose, usibye peptide ya cyclicique, ifite N-terminal (amino-terminal) hamwe na C-terminal (carboxy-terminal).
(2) Itondekanya rya Peptide
Gutondekanya ku nkomoko
Peptide ya endogenous: ikomatanyirizwamo ibinyabuzima ubwayo kandi ikora imirimo itandukanye yumubiri. Neuropeptide, igira uruhare mu kwanduza ibimenyetso no kugenzura muri sisitemu y'imitsi, harimo endorphine na enkephaline, bifite ingaruka zo gusesengura no kugenzura umwuka; imisemburo ya peptide, nka insuline, ningirakamaro muguhuza isukari mu maraso.
Peptide idasanzwe: iboneka mubiryo cyangwa andi masoko yo hanze. Kurugero, poroteyine zimwe na zimwe zirashobora guhindurwa na hydrolyz na enzymes zo mu gifu kugirango zibyare peptide ya bioactive, nka peptide y’amata, ifite imikorere myinshi yumubiri, harimo antioxydeant ningaruka zo kwirinda indwara. Peptide yateguwe binyuze muri synthesis ya chimique cyangwa biotechnologie nayo igwa munsi ya peptide ya exogenous kandi ikoreshwa muburyo bwo guteza imbere imiti no kuvura indwara.
Gutondekanya kubikorwa
Antioxydeant Peptide: Irashobora gukuramo radicals yubusa mumubiri no kugabanya kwangirika kwa okiside iterwa na selile. Kurugero, peptide yumuceri bran anti -xydeant peptide yerekanwe kugirango yongere ibikorwa byimisemburo ya antioxydeant nka catalase (CAT) na glutathione peroxidase (GSH-Px) muri mitochondriya yumutima nubwonko bwimitsi ya D-galactose iterwa nimbeba zashaje, bigabanya urwego rwa mutation ya ADN ya mitochondial mu bwonko, kandi ikingira selile.
Peptide ikingira indwara: Ibi bigenga imikorere yumubiri, byongera cyangwa bigabanya ubudahangarwa bw'umubiri. Peptide zimwe zikomoka ku binyabuzima byo mu nyanja zirashobora gukora ingirabuzimafatizo z'umubiri, zikongerera umubiri ubushobozi bwo kwirinda indwara, kandi zikanafasha mu kurwanya indwara ziterwa na virusi ndetse no gukura kw'ibibyimba.
Gukura kwingirabuzimafatizo ya peptide: Izi ngaruka zigira ingirabuzimafatizo nko gukwirakwiza, gutandukanya, na apoptose. Kurugero, ibintu bikura byindwara (EGF) biteza imbere gukwirakwiza no gutandukanya ingirabuzimafatizo, byihuta gukira ibikomere.
Uruhare rwa peptide mugusaza kwa selile
(1) Kugena imikorere ya mito-iyambere
Mitochondria igira uruhare runini mu gutanga ingufu za selile no guhererekanya ibimenyetso, kandi imikorere idahwitse ifitanye isano no gusaza kwa selile. Peptide ikomoka kuri Mitochondria (MDPs) nka humanin na MOTS-c bigira uruhare runini muguhindura ingirabuzimafatizo. Nyuma ya senescence iterwa no kunanirwa kwinshi, doxorubicin, cyangwa hydrogène peroxide ivura fibroblast yambere yabantu, umubare wa mitochondial uriyongera, urwego rwubuhumekero rwa mitochondial ruzamuka, kandi urwego rwa humanin na MOTS-c narwo ruzamuka. Ubuyobozi bwa humanin na MOTS-c bwongera mu buryo bushyize mu gaciro guhumeka mitochondial mu ngirabuzimafatizo ya doxorubicin iterwa na senescent kandi bigenga igice cya SASP binyuze mu nzira ya JAK, byerekana ko MDPs igira uruhare runini mu mikorere ya mitochondial metabolism no kubyara SASP mu ngirabuzimafatizo za senescent.
Igishushanyo cya 2 Mitochondrial mass nimbaraga zahinduwe mugihe cya senxcence ya doxorubicin. . . Umwanya munini, 20 mm. Ubuso bwa Tom20 bwanditse kuri selile bwapimwe hakoreshejwe ImageJ. (C) Urwego rwa ATP selile murwego rutari senescent (quiescent) na selile. (D) Igipimo cyo gukoresha ogisijeni ya selile (OCR) muri selile zitari senescent na senescent. Ubuhumekero bwibanze, ubushobozi bwubuhumekero busanzwe, hamwe numusaruro wa ATP bibarwa hashingiwe ku guterwa inshinge zikurikiranye ukurikije amabwiriza yabakozwe. (E) Igipimo cya aside irike idasanzwe (ECAR) muri selile zitari senescent (quiescent) na selile.
(2) Ingaruka kumusaza zijyanye no gusaza inzira
p53-p21 inzira
Poroteyine ya p53 ningingo nyamukuru igenga senescence. Iyo selile zihuye nibibazo nko kwangirika kwa ADN, p53 irakora, itera imvugo ya p21, itera ukwezi kwakagari gufatwa mugice cya G1, biganisha kuri senescence. Peptide zimwe na zimwe zirashobora guhindura inzira ya p53-p21, bityo bikagira ingaruka kumajyambere ya senescence. Peptide zimwe na zimwe zirashobora gukorana na poroteyine ya p53, ikabuza ibikorwa byayo bityo igatinda senescence ya selile. Ubushakashatsi bwerekanye ko peptide yihariye ishobora guhagarika imikoranire hagati ya p53 na MDM2 (poroteyine igenga p53), igahindura poroteyine ya p53 kandi ikayigumana kurwego rukwiye kugirango wirinde gukora cyane biganisha kuri senescence.
Inzira ya Rb-E2F
Poroteyine ya Rb ni iyindi poroteyine ngengabuzima igenga poroteyine ihuza na E2F yo kwandikirana kugira ngo ibuze imvugo ya gen. Iyo poroteyine ya Rb iba fosifora kandi idakora, E2F irekurwa, igatera kwinjiza selile mu cyiciro cya S kugirango yigane ADN. Mugihe cya senescence ya selile, impinduka mumuhanda Rb-E2F zitera gufatwa kwinzira. Peptide zimwe na zimwe zirashobora kugenga senescence ya selile muguhindura fosifora ya proteine ya Rb cyangwa bikagira ingaruka kubikorwa bya E2F. Peptide zimwe zishobora kubuza poroteyine ya Rb ya fosifora, ikagumya guhagarara neza kwa Rb-E2F bityo bigatuma gutinda kwa selile.
(III) Amabwiriza ya SASP
SASP igizwe na cytokine zitandukanye, chemokine, na protease, nibindi. Ururenda rwarwo ntirugira ingaruka gusa kuri microen ibidukikije ya selile ya senescent ubwayo ahubwo inagira ingaruka kumubiri no mu ngirabuzimafatizo, bigatera ibisubizo byokongoka hamwe na senescence. Peptide zimwe zishobora kugenzura umusaruro wa SASP no kugabanya ingaruka mbi zayo. Peptide zimwe na zimwe zikomoka ku bimera nazo zabonetse kugenzura SASP mu guhagarika ibikorwa byinzira zerekana ibimenyetso no kugabanya imvugo yibintu bifitanye isano na SASP.
Porogaramu ya Peptide mugutinda gusaza kwa selile
(1) Porogaramu mubicuruzwa byuruhu
Kubera ko abantu benshi bahangayikishijwe no gusaza kwuruhu, peptide yasanze ikoreshwa cyane mubikorwa byo kuvura uruhu. Kurugero, ibicuruzwa bimwe na bimwe byita kuruhu birimo peptide bivuga ko bifite ingaruka zo kurwanya inkari no gutera uruhu. Ubushakashatsi bwerekana ko peptide zimwe zishobora guteza imbere synthesis hamwe no kongera uruhu rworoshye. Peptide irashobora kandi kugenga metabolisme yuruhu rwuruhu, kongera imikorere yinzitizi yuruhu, kugabanya kwangirika kwingirangingo zuruhu ziterwa nimpamvu zituruka kumirasire ya UV, kandi bikadindiza gusaza kwuruhu.
Igishushanyo cya 3 Gusaza mu ruhu ruto kugeza rukuze.
(2) Porogaramu mugutezimbere ibiyobyabwenge
Kuvura Indwara ya Neurodegenerative
Iterambere ry'imiti ya peptide rifite amasezerano akomeye yo gukemura gusaza kwa neuronal mu ndwara zifata ubwonko. Peptide igenga inzira yerekana ibimenyetso byerekana inzira, iteza imbere ubuzima bwa neuronal, kandi yorohereza gusanwa kugirango havurwe indwara ya Alzheimer n'indwara ya Parkinson. Peptide zimwe na zimwe zirashobora kubuza kwegeranya poroteyine zidasanzwe muri neuron, kugabanya neuroinflammation, no gutinda gusaza nurupfu. Peptide yitwa AC-5216 irashobora kubuza kwegeranya poroteyine β-amyloide no kunoza imikorere yubwenge mu mbeba zerekana indwara ya Alzheimer.
Kuvura Indwara z'umutima
Mu kuvura indwara z'umutima-damura, imiti ya peptide irashobora kwibasira inzira ya pathologiya nko gusaza kwa endoteliyale selile no gusaza kwa myocardial. Kurugero, peptide zimwe na zimwe zishobora kugenga imiterere yimitsi yimitsi nimikorere ya selile ya endoteliyale, kunoza gusaza kwingirabuzimafatizo ya endoteliyale, kandi bikagabanya ibyago byindwara zifata umutima. Peptide zimwe na zimwe zirashobora kandi guteza imbere gusana no kuvugurura ingirabuzimafatizo za myocardial, zitanga uburyo bushoboka bwo kuvura indwara nka infirasiyo ya myocardial.
Umwanzuro
Gusaza kwa selile, nkibikorwa bigoye byibinyabuzima, bigira ingaruka kumagara no gusaza kwumubiri. Peptide, nkicyiciro cyingenzi cya molekile ya bioactive, igira uruhare runini muguhuza gusaza ingirabuzimafatizo. Binyuze mu kugenzura imikorere ya mito-iyambere, kwivanga mubusaza bujyanye no gusaza inzira zerekana ibimenyetso, no guhindura SASP, peptide yerekana ubushobozi bwo gutinda gusaza kwa selile.
Inkomoko
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