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1kits （10Ibikoresho）
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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?
Mitochondria, ikora nka 'powerhouse ' ya selile, igira uruhare runini mukubungabunga homeostasis. Uburyo bwitumanaho hagati ya mitochondria na nucleus bumaze igihe byibandwaho mubushakashatsi bwa siyansi. Mitochondria ifite genome yigenga. Kurenga ingirabuzima fatizo zigera kuri 37, ubushakashatsi buherutse gukorwa bwerekanye ko ADN ya mitochondial nayo ikubiyemo peptide ngufi ikora mu binyabuzima, imwe muri zo ikaba ari peptide ikomoka kuri mitochondrial MOTS-c, ikozwe n'akarere ka mitochondrial 12S rRNA. Ubu buvumbuzi bwaguye ku buryo bugaragara imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’imiterere y’ibinyabuzima nka itumanaho rya kirimbuzi na kirimbuzi no kugenzura imikorere ya metabolike.
Kugeza ubu, kuvura indwara nyinshi zitoroshye nka diyabete na hepatite B idakira ihura n'ikibazo gikomeye. Uruhare rukomeye rwa MOTS-c muguhindura imitsi ya skeletale imitsi, nko kongera glucose metabolism, byerekana ubushobozi bwayo mukuvura indwara ziterwa na metabolike. Byongeye kandi, urwego rudasanzwe rwa MOTS-c rwagaragaye mubikorwa bitandukanye byindwara byatumye abashakashatsi bakora ubushakashatsi ku ruhare rwarwo mu gutangira indwara, gutera imbere, no kuvura, bashaka inzira nshya zo gutsinda ibyo bibazo bitoroshye.
Nubuhe buryo bwo gukora kuri MOTS-c?
Kugenga Metabolism-Bifitanye isano Ibimenyetso Inzira
Gukora inzira yerekana ibimenyetso bya AICAR-AMPK: MOTS-c ikora inzira yerekana ibimenyetso bya AICAR-AMPK muguhagarika ingirabuzimafatizo ya folate-methionine. AMPK ikora igenga ingufu za selile metabolism, nko guteza imbere glucose no gufata aside irike. Muri glucose metabolism, byongera guhinduranya glucose itwara glucose GLUT4 kuri membrane selile, bityo bikongerera ubushobozi bwo gufata glucose selile, kunoza insuline, no gufasha mukurinda no kuvura indwara ziterwa na diyabete yo mu bwoko bwa 2 [1].
Ingaruka ku zindi nzira: Kurenga inzira ya AMPK, MOTS-c nayo ikora kumuhanda AKT, inzira ya stress ya okiside, n'inzira zijyanye no gutwika. Kubireba inzira ya AKT, irashobora guhindura inzira ya selile nko gukura, gukwirakwira, no kubaho muguhuza ibikorwa byinzira. Mu nzira ya okiside itera imbaraga, MOTS-C igabanya urugero rwimyuka ya okiside yo mu nda, igabanya ubwoko bwa ogisijeni ikora (ROS), kandi ikarinda selile kwangirika kwa okiside. Mu nzira zijyanye no gutwika, irwanya irekurwa ryabunzi batera umuriro kandi igabanya ibisubizo byokongoka. Kurugero, muburyo bwububabare bukabije, MOTS-C igabanya kurekura mediator yamahembe mumahembe yomugongo yumugongo, bityo bikagaragaza ibimenyetso byububabare [2].
Igicapo 1 Imikorere yibanze ya physiologique ya MOTS-C harimo kugabanya kurwanya insuline, kwirinda umubyibuho ukabije, kunoza imikorere yimitsi, guteza imbere metabolisme yamagufa, kongera imbaraga mumubiri, no gutinda gusaza [1].
Amabwiriza yo Kugaragaza Gene
Amabwiriza agenga imiterere ya nucleaire: Iyo selile zihuye nihungabana rya metabolike, nko guhagarika glucose no guhagarika umutima, MOTS-C ihinduranya nucleus kugirango igenzure neza imiterere ya gene ya kirimbuzi, bityo biteze imbere homeostasis. Kurugero, MOTS-C ihindura imvugo ya genes zijyanye na metabolism nka GLUT4, STAT3, na IL-10, bigira ingaruka kumikorere ya physiologique harimo glucose metabolism no kugenzura immunite. Kwiyongera kwa GLUT4 imvugo byongera glucose selile; STAT3 igira uruhare mu gukwirakwiza selile, gutandukanya, no kugenzura indwara; IL-10, cytokine irwanya inflammatory, igabanya ibisubizo byumuriro mugihe imvugo yayo yazamutse [1,3].
Gutezimbere Metabolism
Glycolysis yongerewe imbaraga: Muburyo butandukanye bwindwara, nkurugero rwibihaha ischemia-reperfusion yimvune (LIRI) iterwa na cardiopulmonary bypass (CPB), kwitegereza MOTS-c byongera umuvuduko wa glycolitike mumyanya mikorobe mikorobe ya endoteliyale (PMVECs). Igabanya imvune ya LIRI mu kugarura ingufu za selile homeostasis no kugabanya lipide peroxidisation binyuze muguhuza urufunguzo rwa glycolitike PFKFB3. Ibi byerekana ko MOTS-c ihindura inzira ya glycolitike kugirango itange ingufu zihagije zingirabuzimafatizo, bityo bikomeze imikorere isanzwe ya selile [4].
Ingaruka zo Kurinda Ingirabuzimafatizo
Kugabanya ibyangiritse bya Mitochondrial: Mu buryo bwerekana imishwarara ya pneumonite (RP), MOTS-c yagabanije cyane imvune y’imitsi y’ibihaha, gutwika, hamwe na stress ya okiside mu gihe ihindura imitekerereze ya alveolar epithelial selile apoptose no kwangirika kwa mitochondial. Ubu buryo bukubiyemo kongera ingufu za kirimbuzi E2 zijyanye na 2 (Nrf2) no guteza imbere itumanaho rya kirimbuzi. Nrf2 ikora urukurikirane rwa antioxydeant na selile ikingira ingirabuzimafatizo, ikingira imikorere ya mito-iyambere. Ibi byerekana ko MOTS-c irinda ingirangingo zangiritse mu kurinda mitochondriya no kugabanya apoptose [5].
Kurinda Izindi selile: Mu bushakashatsi bwakozwe kuri Duchenne muscular dystrofiya (DMD), MOTS-c wasangaga ifite imitsi yibasira imitsi. Yongera imbaraga za glycolytike nubushobozi bwo gutanga ingufu mumitsi ya dystropique, bigira uruhare mumikorere yimitsi. Byongeye kandi, muburyo bwububabare bukabije, MOTS-c yatanzwe hagati cyangwa igabanya kugabanya ububabare bukabije bwububabare mugukumira ibisubizo byumuriro hamwe na hyperexcitability ya neuronal, bitanga ingaruka za neuroprotective [2,6].
Ni ubuhe buryo bukoreshwa na MOTS-c?
Kuvura indwara ziterwa na metabolike:
Kunoza insuline no kwirinda diyabete: MOTS-c yongera imbaraga za insuline, zikaba ari ngombwa mu kwirinda diyabete yo mu bwoko bwa 2. Kurwanya insuline ni ikintu cy'ingenzi mu gutangira diyabete yo mu bwoko bwa 2. MOTS-c irashobora kunoza insuline ikoresheje inzira ya AICAR-AMPK yerekana inzira kandi ikanagenzura ingirabuzimafatizo ya folate-methionine. Ubushakashatsi bwakozwe na Gao Y bwerekana ko butera imitsi ya glucose gufata no kuyikoresha, bisa no gufungura izindi nzira zo kwinjiza glucose mu ngirabuzimafatizo, bityo bikagabanya urugero rwa glucose mu maraso [1].
Kugenga metabolisme ya lipide no kurwanya umubyibuho ukabije: Kubijyanye na metabolisme ya lipide, MOTS-c yongerera ibinure byamavuta ya termogenezi kandi itera amavuta yera. Ibinure byijimye bitwara ingufu binyuze muri thermogenez, mugihe ibinure byera byera bisobanura guhindura amavuta yera abika ingufu mumavuta yumukara ukoresha ingufu. Ubu buryo bufasha umubiri kumenyera ubukonje, kandi cyane cyane, birinda umubyibuho ukabije hamwe n’indwara ya metabolisme ya lipide, bitanga ubumenyi bushya bwo kwirinda no kuvura umubyibuho ukabije [1].
Kwirinda no kuvura indwara ziterwa n'imitsi:
Guteza Imbere Gutandukanya Imitsi: Mu bushakashatsi bwa vitro bwerekana ko ubwoko bwa MOTS-c peptide yo mu gasozi bwongera imiterere ya myotubular mu ngirabuzimafatizo z'umuntu (LHCN-M2) n'imbeba (C2C12) ingirabuzimafatizo, mu gihe peptide Y8F ya mutant idafite ingaruka. Ubushakashatsi bwakozwe bwerekanye ko MOTS-c yongerera myotubulogenez mu gukorana na IL-6 / Janus kinase / transducer ya signal hamwe nogukora inzira ya transcription 3 (STAT3), bityo bikagabanya ibikorwa byo kwanduza STAT3 [7].
Kwirinda imitsi ya Atrophy: Plasma MOTS-c urwego rufitanye isano ribi na myostatine. MOTS-c irinda palotate iterwa na myotube atrophy mu ngirabuzimafatizo zitandukanye za C2C12 kandi igabanya urugero rwa plasma myostatin mu mbeba zifite umubyibuho ukabije. Irinda imitsi iterwa no kongera AKT fosifora, ikabuza ibikorwa bya FOXO1 - ibintu byandikirwa hejuru ya myostatine hamwe nizindi mitsi-atrophy-mugihe igenga ibikorwa bya mTORC2 na PTEN no kongera ibikorwa bya CK2 kugirango ihagarike PTEN [8].
Ingaruka zo kurwanya gusaza: MOTS-c imvugo ihinduka ifitanye isano cyane no gusaza, kandi irerekana imiti irwanya gusaza. Ibi bigerwaho hifashishijwe uburyo bwinshi, harimo kunoza glucose na lipide metabolism, kongera imikorere ya mitochondial selile, no kugabanya umuriro udakira. Ubushakashatsi bwakozwe na Gao Y n'abandi. yerekana ko metabolisme yatezimbere itanga selile nyinshi kandi zihamye zitanga ingufu. Gutezimbere imikorere ya mito-iyambere ni nko kuzamura ingirabuzimafatizo 'uruganda rukora ingufu, ' mugihe kugabanya ibisubizo byumuriro bigabanya kwangirika kwingirabuzimafatizo [1].
Umwanzuro
Nka peptide ikomoka kuri mitochondial, MOTS-c ikora inzira yerekana inzira nka AMPK kugirango igabanye glucose na lipide metabolisme, itume ihinduka ryamavuta yera-yijimye, kandi inoze insuline irwanya umubyibuho ukabije, itanga icyerekezo gishya cyo kuvura indwara ziterwa na metabolike. Yongera itandukaniro rya osteoblast, irwanya imiterere ya osteoclast, iringaniza metabolisme yamagufwa, kandi ishyigikira kubungabunga ubuzima bwamagufwa. Igenga itandukaniro ryimitsi kandi ikarinda atrophy, ifite ubushobozi bwo kwivanga mubibazo biterwa n'imitsi. MOTS-c yerekana amashyirahamwe akomeye ajyanye nimyitozo ngororamubiri: imyitozo ngororamubiri igenga imvugo yayo, kandi ihuza inyungu zatewe nimyitozo ngororamubiri. MOTS-c nayo igira uruhare mugutinda gusaza hamwe nibikorwa bifitanye isano.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru
Ning Ran ni umushakashatsi ukorana na Carlson College of Veterinary Medicine muri kaminuza ya Leta ya Oregon. Ibikorwa bye byamasomo yibinyabuzima bya molekuline nubuvuzi bwubuhinduzi, yibanda ku ngamba zo kuvura indwara zifata ubwonko. Ran yafatanije kwandika ibitabo byinshi mu binyamakuru byasuzumwe n’urungano, agira uruhare mu gusobanukirwa n’imikorere ya molekile mu buryo bw’indwara. Ibyifuzo bye mubushakashatsi birimo guteza imbere no gukoresha peptide-conjugated oligonucleotide, ndetse no gushakisha uburyo bwo kuvura peptide ikomoka kuri mitochondial. Ning Ran yanditse murutonde rwibisobanuro [6].
