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1kits （10Ibikoresho）
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Imiterere ya FOXO4-DRI
Inkomoko: PubChem |
Urukurikirane: LTLRKEPASEIAQSILEAYSQNGWANRRSGGKRPPPRRRQRRKKRG Inzira ya molekulari: C 228H 388N 86O.64 Uburemere bwa molekuline: 5358g / mol PubChem CID: 168431240 Synonyme: EX-A7431 |
Research FOXO4-DRI Ubushakashatsi
Ni ubuhe bushakashatsi bwakozwe na FOXO4-DRI?
Ubushakashatsi bwimbitse kuri Senescence ya Cellular:
Hamwe nubushakashatsi bwimbitse bwimbitse yuburyo bwa senescence ya selile, byagaragaye ko senescence selile igira uruhare runini mubikorwa byinshi bya physiologique kimwe no kubaho no gutera indwara. Ingirabuzimafatizo za Senescent izegeranya kandi zisohora cytokine zitandukanye hamwe n’abunzi batera umuriro, bigira ingaruka ku mikorere y’utugingo ngengabuzima, bityo biganisha ku kugabanuka kwimikorere yimikorere ningingo. Kubwibyo, gushakisha uburyo bwo kwivanga mubikorwa bya senescence ya selile byahindutse ubushakashatsi.
Ivumburwa rya poroteyine ya FOXO4:
FOXO4 ni umwe mubagize agasanduku ka protein O umuryango (FOXO) kandi igira uruhare runini mubikorwa bitandukanye byibinyabuzima nko gukura kw ingirabuzimafatizo, gutandukanya, apoptose, no gukemura ibibazo. Ubushakashatsi bwerekanye ko FOXO4 ifitanye isano rya bugufi na senescence ya selile, kandi irashobora kugira ingaruka kumikorere ya selile muguhindura imvugo ya gen. Kurugero, FOXO4 irashobora gukora imvugo ya genes zimwe na zimwe za antioxydeant hamwe na ADN yo gusana, bikongerera imbaraga ingirabuzimafatizo kurwanya okiside ndetse no kwangirika kwa ADN, bityo bikadindiza senescence.
Kugaragaza ibice bito bya molekile:
Hashingiwe ku gusobanukirwa imikorere ya poroteyine ya FOXO4, abahanga batangiye gusuzuma ibice bito bya molekile bishobora kugenga ibikorwa bya FOXO4. Bizeraga ko bazabona ibintu bito bya molekile bishobora gukora cyane cyane poroteyine ya FOXO4, bityo bikagira ingaruka zo kurwanya gusaza no kuvura indwara zifitanye isano. Nyuma yumubare munini wokugerageza no kugerageza, amaherezo ya molekile ntoya FOXO4-DRI yaje kuvumburwa. Irashobora guhuza cyane na poroteyine ya FOXO4, igakora inzira yayo yerekana inzira yerekana ibimenyetso, kandi ikagira uruhare mukugenzura senescence ya selile hamwe nibikorwa bifitanye isano na physiologique.
Nubuhe buryo bwo gukora bwa FOXO4-DRI?
1. Kurwanya gusaza
FOXO4-DRI irashobora gukora poroteyine ya FOXO4, hanyuma ikagenga metabolisme ya selile, ikwirakwizwa, hamwe na apoptose. Poroteyine ya FOXO4 igira uruhare runini mu kugenzura ingirabuzimafatizo. Irashobora kongera imbaraga zo guhangana ningirabuzimafatizo mukugenzura imiterere yuruhererekane rwa genes zo hepfo, kandi bikagabanya ubukana bwa selile no kwangirika. Kurugero, FOXO4 irashobora guteza imbere imvugo ya enzymes ya antioxydeant kandi ikagabanya urwego rwubwoko bwa ogisijeni itera ingirabuzimafatizo, bityo bikagabanya kwangirika kwa okiside itera selile [1, 2] . Byongeye kandi, FOXO4 irashobora kandi kugenga imvugo ya genes zijyanye na cycle selile, ikabuza ikwirakwizwa ryinshi rya selile, kandi igakomeza metabolism isanzwe nimikorere ya selile.
2. Uburyo bwibikorwa mubagabo batinze-Gutangira Hypogonadism
Imikoranire na FOXO4 na p53:
Abagabo batinze-hypogonadism ni indwara ijyanye n'imyaka, kandi uburyo bwibanze ni imikorere mibi ya selile ya Leydig muri testis. Byagaragaye ko agasanduku k'urupapuro O (FOXO) ibintu byandikirwa FOXO4 bigaragarira cyane mu ngirabuzimafatizo za Leydig, kandi guhinduranya muri nucleus mu bageze mu za bukuru bifitanye isano no kugabanuka kwa synthesis ya testosterone. Nkumwanya wihariye wa FOXO4, FOXO4-DRI ihitamo guhitamo p53 ya kirimbuzi hamwe na apoptose mungirangingo ya senescent Leydig ihagarika imikoranire hagati ya FOXO4 na p53 [1].
Gutezimbere Microen ibidukikije:
Imbeba zimaze gusaza, FOXO4-DRI irashobora guteza imbere mikorobe ya testicular no kugabanya ibura rya testosterone. Ibi byerekana ko FOXO4-DRI ishobora kugarura imikorere isanzwe yumubiri wa testicular muguhuza inzira yerekana ibimenyetso bifitanye isano na senescence ya selile ya Leydig, bityo bikongera urwego rwa testosterone ..
3. Uburyo bwibikorwa muri Fibrosis
Kugabanya Utugingo ngengabuzima no kugabanya imvugo ya SASP:
Indwara ya fibrosis nindwara yibihaha igenda itera inzira yo kuvura. Senescence ya selile ifatwa nkimwe mubintu bitera fibrosis yimpyisi, kandi kurandura ingirabuzimafatizo bishobora kunoza imikorere yibihaha. Muburyo bwimbeba ya fibrosis yimpyisi iterwa na bleomycine, FOXO4-DRI, bisa nibiyobyabwenge byemewe na pirfenidone, birashobora kugabanya ingirabuzimafatizo za senescent, bikagabanya imvugo ya fenotype yibanga ya senescence (SASP), kandi bikagabanya impinduka ziterwa na morphologie hamwe na kolagen ziterwa na bleomycine [2].
Guhindura Igipimo cyubwoko bwakagari:
FOXO4-DRI irashobora kongera igipimo cyubwoko bwa 2 alveolar epithelial selile (AEC2) na fibroblast kandi ikagabanya igipimo cya myofibroblast muburyo bwimbeba ya fibrosis yimpyisi iterwa na bleomycine. Mu bushakashatsi bwa vitro, ugereranije nimbeba n ibihaha byabantu fibroblast selile, FOXO4-DRI ifite imyumvire myinshi yo kwica myofibroblast iterwa no guhindura ibintu bikura-β (TGF-β) [2].
Kugenga Inzira zidasanzwe za Matrix Receptor Imikoranire Inzira:
Ingaruka zo kubuza FOXO4-DRI kuri myofibroblast itera kugabanuka kwa matrise idasanzwe (ECM) reseptor imikoranire yinzira ya bleomycine iterwa na fibrosis. Ibi byerekana ko FOXO4-DRI ishobora kunoza inzira yindwara ya fibrosis yimpaha muguhindura ibisekuru na metabolism ya ECM [2].
FOXO4-DRI itunganya bleomycine (BLM) -indwara ya fibrosis yimpyisi (PF). (A) Igishushanyo mbonera cyerekana igishushanyo mbonera. .
Inkomoko: Byatangajwe [2]
Ni ubuhe buryo bukoreshwa bwa FOXO4-DRI?
1. Kurwanya gusaza
FOXO4-DRI ifite agaciro gashoboka mugutezimbere imyaka igabanuka kumikorere. Hamwe no kwiyongera kwimyaka, ingingo zitandukanye hamwe na sisitemu zitandukanye z'umubiri bizagira uburambe butandukanye bwo gusaza no kugabanuka kumikorere, nko kugabanuka kwimikorere yumubiri, kugabanuka kwimikorere yimitsi yumutima nimiyoboro, ndetse no kugabanuka kwimikorere ya sisitemu. Mugukoresha poroteyine ya FOXO4, FOXO4-DRI irashobora gutinza inzira ya senescence ya selile, kuzamura ubuzima bwimikorere nimikorere, bityo bigafasha kuzamura ubuzima rusange bwumubiri. Kurugero, muburyo bwimbeba yashaje, kuvura hamwe na FOXO4-DRI birashobora kunoza cyane ubushobozi bwimyitozo ngororamubiri n'imikorere yo kumenya imbeba no kugabanya indwara ziterwa n'imyaka [1, 2].
2. Kuvura indwara zifata ubwonko
Isano na Neuron Gusaza n'urupfu:
Indwara zifata ubwonko nk'indwara ya Alzheimer n'indwara ya Parkinson zifitanye isano rya bugufi no gusaza n'urupfu rwa neuron. Muri izo ndwara, neuron izangizwa nimpamvu zitandukanye nka stress ya okiside, igisubizo cyokongoka, hamwe no guteranya poroteyine, biganisha ku gutakaza buhoro buhoro imikorere yimitsi ndetse amaherezo bigatera no guhagarika imikorere yimikorere ya moteri. Mugukoresha inzira ya FOXO4 yerekana inzira, FOXO4-DRI irashobora guteza imbere kubaho no gusana neurone no kongera imbaraga zo guhangana ningutu ya okiside hamwe nibimenyetso bya apoptotique.
Poroteyine ya FOXO4 irashobora kugenga imiterere ya genes nyinshi muri neuron, harimo imisemburo ya antioxydeant, proteyine zirwanya apoptotique, ibintu bikura mu mitsi, n'ibindi. Kurugero, muburyo bwimbeba yindwara ya Alzheimer, kuvura hamwe na FOXO4-DRI birashobora kugabanya kwinjiza poroteyine za amyloide, kunoza imikorere ya neuronal, no kudindiza iterambere ryindwara. Mu buryo bw'indwara ya Parkinson, FOXO4-DRI irashobora kandi kurinda neuron ya dopaminergique no kunoza ubushobozi bwo gukora imbeba [3, 4] . Kubera iyo mpamvu, FOXO4-DRI biteganijwe ko izakoreshwa mu kuvura indwara zifata ubwonko kugira ngo bidindiza iterambere ry’indwara no kunoza imikorere y’ubwenge n’imodoka by’abarwayi.
3. Kwirinda no kuvura indwara zifata umutima
Kurinda Cardiomyocytes:
Muri sisitemu yumutima nimiyoboro y'amaraso, FOXO4-DRI irashobora kurinda kardiomyocytes kwirinda guhagarika umutima no kwangirika kwa apoptotique. Cardiomyocytes ningirabuzimafatizo zingenzi zumutima, kandi kwangirika kwabo nurupfu nimwe mumpamvu zingenzi zitera indwara z'umutima. FOXO4-DRI irashobora gukora poroteyine ya FOXO4, igenga imiterere yimisemburo ya antioxydeant, ikagabanya urwego rwimiterere ya ogisijeni yo mu bwoko bwa ogisijeni iterwa na kardiomyocytes, kandi ikagabanya kwangirika kwingutu ya okiside kuri cardiomyocytes. Muri icyo gihe, FOXO4-DRI irashobora kandi guteza imbere imvugo ya poroteyine zirwanya apoptotique, ikabuza gukora inzira yerekana ibimenyetso bya apoptotique, kandi ikarinda umutima wa kanseri ya apoptose [4].
Gutezimbere Imikorere y'utugingo ngengabuzima twa Endothelia:
FOXO4-DRI irashobora kandi guteza imbere imikorere isanzwe ya selile endoteliyale yimitsi kandi ikagumya gutuza no gukomera kwimitsi yamaraso. Utugingo ngengabuzima twa endoteliyale ni igice cyingenzi cyurukuta rwamaraso, kandi imikorere yabyo idasanzwe izatuma habaho indwara zifata umutima nimiyoboro y'amaraso nko kwiyongera kwimitsi y'amaraso, trombose, na aterosklerose. FOXO4-DRI irashobora gukora poroteyine ya FOXO4, igenga imiterere ya genes nyinshi mu ngirabuzimafatizo ya endoteliyale, igatera ikwirakwizwa, kwimuka, no gusana ingirabuzimafatizo ya endoteliyale, kandi igakomeza imikorere isanzwe y'imiyoboro y'amaraso. Kurugero, FOXO4-DRI irashobora kugenzura imvugo yikura ryimitsi iva mu mitsi (VEGF), igatera ikwirakwizwa ryingirabuzimafatizo ya endoteliyale na angiogenez; irashobora kandi kugenga imvugo ya synthase ya nitric okiside ya endoteliyale (eNOS), igatera imbere kubyara aside nitide, kwagura imiyoboro yamaraso, no kugabanya umuvuduko wamaraso [4].
Kwirinda no kuvura indwara z'umutima n'imitsi:
Muri make, FOXO4-DRI ifasha mukurinda no kuvura indwara zifata umutima nimiyoboro yamaraso nka infarction myocardial, kunanirwa k'umutima, na aterosklerose. Muburyo bwinyamanswa yindwara ya myocardial, kuvura hamwe na FOXO4-DRI birashobora kugabanya urupfu rwa cardiomyocytes, bigateza imbere gusana ingirangingo za myocardial, no kunoza imikorere yumutima. Muburyo bwo kunanirwa k'umutima, FOXO4-DRI irashobora kubuza apoptose ya cardiomyocytes, kongera ubwonko bwa myocardial, no kunoza imikorere yo kuvoma umutima. Muri moderi ya aterosklerose, FOXO4-DRI irashobora kugabanya kwangirika kwingirabuzimafatizo ya endoteliyale, ikabuza kwifata, kandi bikagabanya ibyago byo kurwara aterosklerose [4].
Mu gusoza, binyuze muburyo bwayo bwibikorwa, harimo gutera apoptose yingirabuzimafatizo ya senescent, kunoza imitekerereze ya mikorobe, no gutinda gusaza, FOXO4-DRI yerekana agaciro gakoreshwa mubijyanye no kurwanya gusaza, kuvura hypofonction testicular, fibrosis iterwa nimirasire, indwara zifata ubwonko, no kwirinda no kuvura indwara zifata umutima.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru
Han X ni umushakashatsi ufatanije n’ibigo byinshi by’icyubahiro, birimo Ishuri Rikuru ry’Ubumenyi rya Jiangxi, Kaminuza ya Fudan, Kaminuza ya Hunan, Kaminuza ya Zhengzhou, Kaminuza ya Geosciences, Kaminuza ya Sichuan, Kaminuza y’igihugu ya Singapuru, Minisiteri y’umutungo kamere wa Repubulika y’abaturage, Ishuri Rikuru ry’Ubuvuzi rya Peking, Ishuri Rikuru ry’Ubuvuzi rya Peking, Ishuri Rikuru ry’Ubuvuzi rya Peking, Kaminuza ya Tianjin, na Kaminuza isanzwe y'Amajyaruguru -. Ihuriro ryerekana amateka ye menshi kandi atandukanye.
Inyungu zubushakashatsi bwe zikubiye mubyiciro byinshi byingenzi. Akora cyane mubushakashatsi mubijyanye na Chimie, Ubumenyi bwibidukikije & Ibidukikije, Ubushakashatsi & Medicine Experimental Medicine, Oncology, na Biochemie & Molecular Biology. Ibikorwa bye byerekana ubuhanga bwagutse nintererano zikomeye muri utwo turere. Han X yanditse ku rutonde rwerekana [2].
