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▎ MOTS-c Imiterere
Inkomoko: PubChem |
Urukurikirane: MRWQEMGYIFYPRKLR Inzira ya molekulari: C101H152N28O22S2 Uburemere bwa molekuline: 2174.6g / mol Numero ya CAS: 1627580-64-6 CID CID: 146675088 Synonyme: UNII-A5CV6JFB78 |
▎ MOTS-c Ubushakashatsi
Ni ubuhe bushakashatsi bwakozwe na MOTS-c?
Mitochondrion ni urubuga rukomeye rwo guhinduranya ingufu mu ngirabuzimafatizo. Kuva kera, abahanga bakoze ubushakashatsi bwimbitse kandi bwimbitse ku miterere n'imikorere ya mitochondria. Muri iki gikorwa, byamenyekanye buhoro buhoro ko mitochondriya itagira uruhare runini mu kubyara ingufu gusa ahubwo ishobora no kugira uruhare mubindi bikorwa byimikorere ya selile binyuze muburyo butazwi.
Hamwe niterambere ryiterambere ryikoranabuhanga ryubushakashatsi, cyane cyane iterambere rya genomics na proteomics, byashobokaga kuvumbura molekile nshya zijyanye na mitochondria. MOTS-c (ikarito ya mitochondrial ifunguye yo gusoma ya 12S rRNA-c) ni peptide ikomoka kuri mitochondriya ikozwe na 12S rRNA yo mu karere ka genoside ya mitochondial [1].
Binyuze mu isesengura ryimbitse rya genoside ya mitochondrial, abahanga bavumbuye uduce duto duto two gusoma (sORFs), dushobora gushiramo peptide zimwe na zimwe zifite imirimo yihariye. Nyuma yubushakashatsi nubugenzuzi, MOTS-c yamenyekanye. Ubushakashatsi bwerekanye ko MOTS-c igaragarira mu ngingo zitandukanye mu bantu no ku nyamaswa. Ikora cyane cyane ku mitsi ya skeletale ikoresheje amaraso, ikongerera gufata no gukoresha glucose, bityo bigatuma insuline irwanya kandi ikanagabanya imiterere ya metabolike ..
Hamwe n’ubushakashatsi bwimbitse, byagaragaye ko impinduka mu mvugo ya MOTS-c zifitanye isano rya bugufi no kubaho no guteza imbere gusaza n'indwara ziterwa n'imyaka. Kurugero, urwego rwa MOTS-c muri plasma rugabanuka uko imyaka igenda ishira (Zheng Y, 2013). Muri icyo gihe, byagaragaye ko MOTS-c ari ingirakamaro ku ndwara ziterwa n'imyaka, harimo diyabete, indwara z'umutima n'imitsi, osteoporose, umubyibuho ukabije nyuma yo gucura, n'indwara ya Alzheimer [3].
Nubuhe buryo bwo gukora bwa MOTS-c?
Kugena imvugo ya gene:
MOTS-c irashobora gukoresha imikorere yayo ya physiologique muguhuza imvugo ya gene. Kurugero, irashobora kugenga imvugo ya gen nka GLUT4, STAT3, na IL-10. MOTS-c igira uruhare runini mugukoresha inzira yerekana ibimenyetso bya AICAR-AMPK no guhagarika inzitizi ya folate-methionine mu tugari [4].
Kunoza insuline irwanya:
MOTS-c irashobora kugabanya kurwanya insuline no kwirinda diyabete yo mu bwoko bwa 2. Uburyo bwibikorwa bushobora kuba bujyanye no kubuza myostatine. Ubushakashatsi bwerekanye ko plasma MOTS-c ifitanye isano mbi nurwego rwa myostatine mumubiri wumuntu. MOTS-c irashobora kunoza insuline mu guhagarika ibikorwa byurwego rwo hejuru rwo kwandukura FOXO1 no kugabanya urwego rwa myostatine [5].
Guteza imbere gutandukanya imitsi:
Mu ngirangingo z'imitsi, MOTS-c ikorana na STAT3 ikoresheje moteri ya SH2 ihuza motif mu karere ka YIFY, igabanya ibikorwa byo kwanduza STAT3, bityo bikazamura myotube. Ubwoko bwa gasozi MOTS-c peptide irashobora kongera imiterere ya myotube yumuntu (LHCN-M2) nimbeba (C2C12) ingirabuzimafatizo ya progenitor kandi ikarinda ingirangingo z'imitsi kugabanuka kwa myogenine ya kirimbuzi iterwa na interleukin-6 (IL-6) [6].
Kugenga imikorere ya mitochondial:
MOTS-c irashobora kugenga metabolism ya mitochondial. Ubushakashatsi bwerekanye ko kuvura ingirangingo z’inyamabere hamwe na MOTS-c bishobora kongera urugero rwa poroteyine y’ibimenyetso bya mitochondrial biogenezi ya TFAM, COX4, na NRF1, ariko isesengura rya cytometrie ryerekana ko umubare wa mitochondriya ugabanuka cyane nyuma yo kuvura MOTS-c. Ubushakashatsi bwakozwe bwerekanye ko MOTS-c ishobora guhuza ibikorwa bya mitochondial kandi ikongera urugero rwa poroteyine ya GTPase ebyiri, OPA1 na MFN2, zikaba ari ingenzi cyane mu guhuza mitochondriya y’inyamabere. Guhagarika GTPase ebyiri cyangwa gukubita MFN2 ukoresheje siRNA bizakuraho ubushobozi bwa MOTS-c bwo guteza imbere GLUT4 guhinduranya no gufata glucose [7].
MOTS-c ni intego yo kuvura indwara nyinshi ziterwa no gusaza, harimo neurodegeneration, osteoporose, indwara zifata umutima, aterosklerose, sarcopenia, diyabete yo mu bwoko bwa 2, n'umubyibuho ukabije.
Inkomoko: Byatangajwe [8]
Ni ubuhe buryo bukoreshwa na MOTS-c?
Kunoza indwara ziterwa n'imyaka
Isano no gusaza:
MOTS-c ni peptide ikomoka kuri mitochondriya, kandi impinduka mu mvugo zayo zifitanye isano rya bugufi no kubaho no gutera imbere gusaza n'indwara ziterwa n'imyaka. Mugihe abantu basaza, urwego rwa MOTS-c rugabanuka. Ubushakashatsi bwerekanye ko imyitozo igira ingaruka zikomeye ku mvugo ya MOTS-c, kandi MOTS-c ishobora guhuza ingaruka zo kurwanya gusaza imyitozo [3].
Diyabete:
MOTS-c irashobora kunoza glucose yumubiri hamwe na metabolisme ya lipide, igateza imbere imikorere ya mitochondial selile, kandi ikagabanya uburyo bwa chronique idakira. Ku barwayi ba diyabete, urwego rwa MOTS-c muri plasma rugabanuka. MOTS-c irashobora kugenga homeostasis metabolike yihutisha gufata glucose no kunoza insuline, kandi igira ingaruka nziza mukurinda diyabete yo mu bwoko bwa 2 [8].
Indwara z'umutima n'imitsi:
Kuvugurura imitima yumutima no kudakora neza nibibazo bisanzwe bya diyabete, akenshi biganisha kumutima ukomeye. MOTS-c irashobora kunoza imikorere ya endoteliyale yimitsi kandi ni intego nshya yo kuvura indwara zifata umutima na diabete. Ubushakashatsi bwerekanye ko MOTS-c ishobora gusana myocardial mitochondrial yangiritse ku mbeba za diyabete kandi ikarinda imikorere yimitsi yumutima na diastolique [9].
Osteoporose: MOTS-c irashobora guteza imbere ikwirakwizwa, gutandukana, hamwe nubutaka bwa osteoblasts, bikabuza gene osteoclast, kandi bikagenga metabolisme yamagufwa no guhindura amagufwa. Imyitozo ngororamubiri irashobora kugenzura neza imvugo ya MOTS-c, ariko uburyo bwihariye imyitozo igenga MOTS-c mu magufwa ntibirasobanuka neza [10].
Izindi ndwara
Fibrosis yo mu bihaha:
Fibrosis yo mu bihaha ni indwara ikomeye y'ibihaha hamwe no kutamenya neza, kandi etiologiya yayo na patogenezi yayo ntibirasobanuka neza. Mitochondrial ifunguye yo gusoma ya 12S rRNA-c (MOTS-c) ni peptide yashizwemo na genome ya mitochondrial, igira ingaruka nziza kuri metabolisme ya glucose na lipide, homeostasis ya selile na mitochondrial homeostasis, no kugabanya uburyo bwo gutwika sisitemu, kandi birashobora kuba imyitozo yigana. Iri suzuma rigamije gusesengura byimazeyo ubuvanganzo buriho ku ruhare rwa MOTS-c mu kuzamura iterambere rya fibrosis yo mu bihaha no kumenya intego zihariye zo kuvura ingamba zo kuvura ejo hazaza [11].
Duchenne imitsi ya dystrofiya:
MOTS-c ni mitochondriya ikomoka kuri bioactive peptide ifite imiterere yihariye yibasira imitsi, ishobora kongera umuvuduko wa glycolytike hamwe nubushobozi bwo gutanga ingufu zimitsi ya dystrofique muri vitro no muri vivo, bityo bikazamura ibikorwa nibikorwa bya fosifonodiamidite morpholino oligomers (PMO) mumbeba za mdx. Imiyoborere miremire isubirwamo ya MOTS-c na PMO irashobora gutuma habaho urwego rwo kuvura dystrofine mumitsi ya periferique, kunoza imikorere yimitsi na patologiya yimbeba za mdx, kandi nta burozi bugaragara [12].
Umubyibuho ukabije n'imitsi:
Umubyibuho ukabije na diyabete yo mu bwoko bwa 2 ni indwara ziterwa na metabolike akenshi zijyana na sarcopenie no kudakora neza kw'imitsi. MOTS-c, nka hormone itunganijwe, igira uruhare muri metabolic homeostasis. Ubushakashatsi bwerekanye ko plasma MOTS-c ifitanye isano mbi nurwego rwa myostatine mumubiri wumuntu. MOTS-c irashobora gukumira aside palmitike iterwa na atrophy ya myotubes ya C2C12 itandukanye kandi ikagabanya urugero rwa myostatine muri plasma yimbeba ziterwa numubyibuho ukabije. Muguhagarika myostatine, MOTS-c irashobora kuba uburyo bwo kuvura imitsi ya skeletale iterwa no kurwanya insuline hamwe nizindi fenotipike yimitsi irimo sarcopenie [5].
Ibyago byindwara ziterwa na kanseri yamabere:
Abagore bakiriye kanseri y'ibere bafite ibyago byinshi byo kwandura indwara z'umutima n'imitsi, diyabete, n'umubyibuho ukabije, kandi imyitozo ngororamubiri irashobora kugabanya izo ngaruka. MOTS-c ifite ibikorwa byo kwigana imyitozo kandi bigira ingaruka nziza kuri metabolism hamwe nubushobozi bwimyitozo ngororamubiri. Ubushakashatsi bwerekanye ko ibyumweru 16 by’imyitozo ngororamubiri yo mu kirere no kurwanya indwara bishobora kongera urwego rwa MOTS-c ku barokotse kanseri y'ibere itari Hisipaniya, ariko nta ngaruka nini zigira ku barokotse kanseri y'ibere ya Hisipaniya. Ubwiyongere bw'urwego rwa MOTS-c buterwa n'imyitozo ngororamubiri ku barokotse kanseri y'ibere itari Hisipaniya bishobora kuba bifitanye isano no kunoza insuline, bityo bikagabanya ibyago byo kwandura [13].
Mu gusoza, nka 16-amino acide polypeptide yashizwemo na genoside ya mitochondrial, MOTS-c igira uruhare runini muguhindura umubiri, kugenzura imihangayiko, no kwirinda indwara no kuvura. Irashobora guteza imbere cyane homeostasis ya glucose na lipide metabolism, ikongerera insuline ibyiyumvo, kandi ikabuza imvugo ya myostatine, igabanya neza diyabete yo mu bwoko bwa 2, umubyibuho ukabije, hamwe na atrophyi yimitsi ifitanye isano. Muri icyo gihe kandi, mu kugenzura ibinyabuzima bya mitochondrial biogenezi no guhuza, MOTS-c yongerera imbaraga antioxydeant selile kandi ikabuza igisubizo cy’umuriro, ikerekana ubushobozi bwo kuvura indwara zidakira nk'indwara z'umutima n'imitsi, osteoporose, na fibrosis. By'umwihariko, nkumuhuza wingenzi witumanaho rya mitochondria-nucleus, MOTS-c irashobora kwigana ingaruka zimyitozo ngororamubiri no gutinda gusaza. Urwego rwarwo rufitanye isano ribi n'indwara ziterwa n'imyaka, kandi inyongera ya exogenous irashobora guhindura imiterere ya metabolike kandi ikabuza kwandura virusi. Bizwi nka 'imisemburo ya mitochondrial '.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru
Dieli-Conwright CM ni intiti ifite uruhare runini mubice bitandukanye bya oncology na siporo yubumenyi. Kugeza ubu ni umwarimu wungirije w’ubuvuzi mu Ishuri Rikuru ry’Ubuvuzi rya Harvard n’Ikigo cya Dana-Farber Kanseri kandi afite umwanya w’ishami wungirije mu ishami ry’imirire mu ishuri ry’ubuzima rusange rya Harvard TH Chan. Ubushakashatsi bwa Dr. Dieli-Conwright bwibanze ku kumenya ingaruka z’imyitozo ngororamubiri ku barwayi ba kanseri, cyane cyane uburyo imyitozo ishobora kuzamura imikorere y’imiterere, ubuzima bw’amagufwa, ndetse n’ubuzima bw’abarwayi ba kanseri. Amashuri yize akubiyemo ibintu byinshi nka biologiya, kinesiologiya, ubuzima rusange, na biokinesiology. Yarangije amasomo ye mu bigo nka kaminuza ya Leta ya Californiya, Northridge, na kaminuza y’Amajyepfo ya Californiya kandi arangiza ubushakashatsi bwe bwa dogiteri mu kigo cy’ubuvuzi cya City of Hope. Ubushakashatsi bwa Dr. Dieli-Conwright bwagiye busohoka cyane mu binyamakuru bitandukanye by’amasomo, kandi umurimo we urimo amasomo menshi nk'ubuzima rusange, imirire, sisitemu y'umutima n'imitsi, ndetse n'indwara z'umutima, bitanga ibimenyetso bifatika bya siyansi bijyanye no gusubiza mu buzima busanzwe no gucunga ubuzima bw'abarwayi ba kanseri. Dieli-Conwright CM yashyizwe ku rutonde rwerekana [13].
