MOTS-c txhaj, Nws yog mitochondrial derived peptide encoded los ntawm mitochondrial genome. Nws yog peptide me me uas muaj 16 amino acids nrog cov qauv me me me me, uas tso cai rau nws kom nthuav dav hauv cov hlwb thiab cuam tshuam nrog ntau lub hom phiaj intracellular. Qhov hnyav molecular yog kwv yees li 2174.62 (txoj kev suav sib txawv yuav txawv me ntsis). Nws feem ntau muaj nyob rau hauv daim ntawv khov- cov hmoov qhuav, nrog rau cov tsos zoo, qhov kub thiab txias ntawm -20 ° C, thiab qhov ceev ntawm 1.44 ± 0.1 g / cm³ (tus nqi kwv yees). Mitochondria feem ntau suav hais tias yog "cov chaw tsim hluav taws xob" ntawm cov hlwb, muaj peev xwm tsim cov tshuaj lom neeg peptides ntxiv rau lawv txoj haujlwm ntawm kev tsim hluav taws xob. Tom qab synthesis hauv mitochondria, nws raug tso tawm mus rau hauv lub cell kom ua haujlwm rau nws. Nws tau tshawb pom raws li qhov kev nce qib tshiab tshaj plaws hauv kev daws teeb meem sib luag thev naus laus zis, thiab ntau yam peptides tshwj xeeb tau muab los ntawm mitochondrial genome tau txheeb xyuas, suav nrog MOTS c.
Peb cov khoom
Cov ntaub ntawv ntxiv ntawm chemical compound:
Peb Cov Khoom
MOTS-c+. COA
Tshawb nrhiav hauv cov qauv kab mob metabolic
Mob Ntshav Qab Zib Model
Hauv cov qauv ntshav qab zib, MOTS c tuaj yeem txhim kho insulin tsis kam thiab tswj ntshav qabzib. Piv txwv li, hauv cov txiv neej Sprague Dawley nas qauv ntawm hom 2 mob ntshav qab zib, MOTS c (0.5 mg / kg; txhaj tshuaj intraperitoneal; Ib hnub; 8 lub lis piam) tuaj yeem txo cov ntshav qabzib sai, glycosylated serum protein, thiab ntshav lipid qib, txhim kho myocardial ultrastructure puas, thiab qhib cov tshuaj tiv thaiv kab mob myocardial AMPK/Nrf2.
Obesity Model
MOTS c tuaj yeem txo cov rog rog uas tshwm sim los ntawm - noj zaub mov rog. Nws tuaj yeem inhibit qhov kev qhia ntawm cov noob roj synthesis thiab txhawb cov piam thaj metabolism, yog li pab txo qhov hnyav thiab rog.
Kev tshawb fawb hauv cov qauv kab mob plawv
Myocardial ischemia-reperfusion raug mob (MIRI) qauv
Hauv MIRI qauv,MOTS-c txhajtuaj yeem txhawb mitochondrial biosynthesis hauv myocardial hlwb, inhibit myocardial cell apoptosis, thiab txhim kho myocardial raug mob hauv MIRI nas. Nws cov txheej txheem yuav cuam tshuam txog kev tswj hwm PGC-1 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha) Qhia txog kev cuam tshuam. PGC-1 yog qhov tseem ceeb ntawm kev tswj hwm hauv mitochondrial biosynthesis thiab kev ua haujlwm. MOTS c txhawb nqa mitochondrial biosynthesis thiab kev ua haujlwm rov qab los ntawm kev txhawb nqa kev qhia ntawm PGC-1, yog li txo qis kev raug mob ntawm myocardial.
Kab mob plawv Coronary (CHD) qauv
MOTS c muaj kev tiv thaiv kev ua haujlwm ntawm endothelial thiab tuaj yeem cuam tshuam kev loj hlob ntawm atherosclerosis. Tam sim no nws yog lub hom phiaj tshiab rau kev kuaj mob thiab kho CHD.
Kev tshawb fawb hauv cov qauv kab mob siab
Hauv cov qauv uas tsis yog- cawv steatohepatitis (NASH), ib pab neeg tshawb fawb los ntawm Lub Tsev Kawm Ntawv Qib Siab Fourth Military Medical University pom tias MOTS c tuaj yeem ua rau muaj kev ruaj ntseg ntawm Bcl-2 protein thiab inhibit ubiquitination, yog li inhibiting kev loj hlob ntawm NASH. Piv nrog rau pawg tswj hwm, cov nas uas kho nrog MOTS c tau qis lub cev hnyav thiab lub siab lub cev hnyav dua, thiab MOTS c kev kho mob cuam tshuam rau hepatic steatosis thiab inhibited loj lipid droplet deposition. TUNEL staining thiab F4/80 thiab aSMA immunoblotting tsom xam pom tias MOTS c kev kho mob tuaj yeem txo qhov kev loj hlob ntawm daim siab cell apoptosis, o, thiab fibrosis. Tsis tas li ntawd, MOTS c cuam tshuam qhov kev qhia ntawm pro-inflammatory, pro fibrotic, thiab DNA sensing noob los ntawm NASH. Ntxiv nrog rau kev txo cov rog hauv daim siab, MOTS c kev kho mob kuj tseem cuam tshuam qhov kev qhia ntawm cov noob roj synthesis.
Kev tshawb fawb hauv Cov Qauv Kab Mob Neurological
Hauv kev raug mob lub hlwb tus qauv ntawm cov txiv neej C57BL / 6 nas, MOTS c (25-50 mg / kg; intraperitoneal txhaj; Ib hnub; 21 hnub) tuaj yeem txo qis cov paj hlwb thiab inhibit HMGB1 / TLR4 / NF - κ B inflammatory pathway nyob rau hauv lub hlwb.
Kev tswj cov tshuaj insulin rhiab heev
Nws tuaj yeem tswj cov tshuaj insulin rhiab heev thiab txhawb nqa cov piam thaj. Hauv cov qauv ntawm tes ntawm insulin tsis kam, Nws tuaj yeem txhim kho lub cell teb rau insulin, tso cai rau lub cell kom zoo dua thiab siv cov piam thaj, zoo li qhib lub "qhov rooj" rau lub cell kom tau txais cov khoom noj. Piv txwv li, hauv cov ntshav ntawm cov neeg mob ntshav qab zib lossis rog rog, qib ntawm MOTS c tau txo qis, uas qhia tau hais tias nws muaj feem cuam tshuam nrog insulin tsis kam thiab cov piam thaj tsis sib xws.
Koom nrog kev tswj hwm ntawm fatty acid oxidation
Nws koom nrog hauv kev tswj hwm ntawm fatty acid oxidation thiab pab tswj qhov sib npaug ntawm intracellular lipid metabolism. Nws tuaj yeem khi rau cov receptors ntawm adipocyte daim nyias nyias, txhawb kev nthuav qhia ntawm cov piam thaj thauj cov noob, pab txhawb cov piam thaj metabolism, thiab inhibit qhov kev qhia ntawm cov rog synthesis noob, yog li txo cov rog deposition vim siab - noj cov rog.
Anti-inflammatory nyhuv
Inhibit qhov kev qhia ntawm inflammatory yam
Nws inhibits qhov kev qhia ntawm pro-inflammatory cytokines (TNF - , IL-6, IL-1 ) thiab txhawb cov kev qhia ntawm anti-inflammatory cytokine (IL-10) los ntawm suppressing lub MAPK signaling txoj kev thiab txhim kho lub Ahr / STAT3 signaling pathway. TNF - thiab IL-6 yog ob qho tib si tseem ceeb uas cuam tshuam rau atherosclerosis. Clinically, theem ntawm IL-6 nyob rau hauv cov ntshav ntawm cov neeg mob uas muaj kab mob plawv (CHD) tau nce ntau, thiab MOTS c tuaj yeem txo cov tshuaj tiv thaiv kab mob los ntawm kev tswj cov kev qhia ntawm cov kab mob inflammatory.
Inhibit qhov ua kom ntawm inflammatory signaling txoj kev
Kev ua kom ntawm MAPK / NF kB txoj hauv kev yuav cuam tshuam rau kev nthuav qhia ntawm ntau cov adhesion molecules thiab ntau yam inducible enzymes (COX2, iNOS), thiab koom nrog qhov tshwm sim ntawm endothelial dysfunction. Nws yuav inhibit qhov kev loj hlob ntawm o los ntawm kev tswj cov teeb liab txoj kev, yog li tiv thaiv endothelial muaj nuj nqi thiab ncua qhov tshwm sim ntawm atherosclerosis.
Regulating cellular aging phenotype
Kev tshawb fawb tau pom tias MOTS c muaj feem cuam tshuam nrog kev laus. Nws tuaj yeem tswj cov kev laus phenotype ntawm cov hlwb, ncua kev laus ntawm tes los ntawm kev txhim kho cellular metabolism thiab muaj peev xwm teb kev ntxhov siab. Hauv qee cov qauv kev sim biology, nce qib ntawm MOTS c tuaj yeem ua kom lub neej ntev ntawm cov kab mob, uas tuaj yeem ua tiav los ntawm kev ua kom muaj kev tiv thaiv kab mob tiv thaiv - cov noob laus thiab cov kev taw qhia.
Txhim kho mitochondrial mediated metabolic ntshawv siab
Hauv cov kab mob xws li tsis yog -alcoholic steatohepatitis (NASH), nws kev kho mob txhim kho mitochondrial mediated metabolic disorders hauv NASH. Carnitine shuttle, tricarboxylic acid voj voog, thiab degradation cov tshuaj tiv thaiv muaj feem xyuam rau cov amino acid thiab urea metabolism tag nrho koom nrog enzyme dependent tshuaj nyob rau hauv lub mitochondrial matrix, uas yog ib qho tseem ceeb rau kev tswj mitochondrial homeostasis. Metabolomics tsom xam pom tias MOTS c kev kho mob ib nrab thim rov qab qhov txo qis ntawm cov metabolites tseem ceeb hauv cov acylcarnitine shuttle txoj kev tshwm sim los ntawm NASH. Cov metabolites nruab nrab tseem ceeb hauv lub voj voog urea thiab tricarboxylic acid lub voj voog raug cuam tshuam raws li NASH cov xwm txheej thiab txhim kho tau zoo tom qab MOTS c kho.
Antioxidant kev nyuaj siab
Thaum cov hlwb raug kev nyuaj siab, xws li oxidative kev nyuaj siab, qhia theem ntawm MOTS c hloov. Nws tuaj yeem ua kom muaj kev ntxhov siab hauv cov hlwb, ua rau muaj kev nthuav tawm ntawm cov enzymes antioxidant, pab cov hlwb tshem tawm cov dawb radicals ntau dhau, txo oxidative puas tsuaj, thiab yog li tiv thaiv cell kev ncaj ncees thiab ua haujlwm. Piv txwv li, nyob rau hauv oxidative kev nyuaj siab,MOTS-c txhajtuaj yeem ua rau kev nthuav tawm ntawm cov enzymes antioxidant thiab txhim kho lub peev xwm antioxidant ntawm cov hlwb.
Clinical application prospects
Mob ntshav qab zib hom 2
Muab lub luag haujlwm ntawm MOTS c hauv kev tswj cov tshuaj insulin rhiab heev thiab cov piam thaj metabolism, nws muaj peev xwm siv tau tus nqi hauv kev kho mob ntshav qab zib hom 2. Los ntawm kev tswj hwm txoj kev taw qhia cov tshuaj insulin thiab txhawb nqa cov piam thaj, MOTS c txhaj tshuaj tuaj yeem pab txo cov ntshav qab zib thiab txhim kho cov tsos mob hauv cov neeg mob ntshav qab zib.
rog rog
Nws tuaj yeem cuam tshuam qhov kev qhia ntawm cov noob roj synthesis, txhawb cov piam thaj metabolism, txo cov rog rog, thiab yog li ntawd tuaj yeem ua lub luag haujlwm hauv kev kho mob rog. Los ntawm kev tswj hwm lub zog metabolism sib npaug, MOTS c txhaj tshuaj tuaj yeem pab txo qhov hnyav thiab txhim kho kev rog rog ntsig txog metabolic.
kab mob plawv
Nws muaj lub peev xwm los tiv thaiv endothelial muaj nuj nqi thiab inhibit qhov kev loj hlob ntawm atherosclerosis, ua rau nws yog ib tus neeg sib tw zoo rau kev kho mob thiab tiv thaiv kab mob plawv. Los ntawm kev tswj cov kev qhia ntawm cov kab mob inflammatory thiab cov kev taw qhia, MOTS c txhaj tshuaj tuaj yeem pab txo qis cov hlab ntsha, ua kom cov plaques ruaj khov, thiab txo cov kev pheej hmoo ntawm cov kab mob plawv.
myocardial infarct
Hauv myocardial ischemia-reperfusion raug mob qauv, nws nthuav tawm cov txiaj ntsig ntawm mitochondrial biosynthesis thiab inhibiting myocardial cell apoptosis, uas tuaj yeem ua lub luag haujlwm hauv kev kho mob myocardial infarction. Los ntawm kev tiv thaiv myocardial hlwb, nws yuav pab txhim kho myocardial muaj nuj nqi thiab txo cov teeb meem tom qab myocardial infarction.
Hauv cov tsis yog - cawv steatohepatitis thiab lwm yam kab mob, Nws tuaj yeem txhim kho mitochondrial mediated metabolic disorders, alleviate the process of hepatic steatosis, apoptosis, o, and fibrosis, thiab yog li ntawd tej zaum yuav muaj txiaj ntsig zoo hauv kev kho mob siab. Los ntawm kev tswj hwm cov metabolism thiab cov lus teb ntawm lub siab, MOTS c txhaj tshuaj tuaj yeem pab txhim kho daim siab ua haujlwm thiab ncua kev loj hlob ntawm daim siab kab mob.
Hauv cov qauv ntawm cov kab mob neurological xws li kev puas hlwb raug mob, MOTS c nthuav tawm lub luag haujlwm hauv kev txo qis cov paj hlwb thiab inhibiting inflammatory pathways, yog li muaj peev xwm muaj peev xwm siv tau rau hauv kev kho cov kab mob neurological. Los ntawm kev tiv thaiv cov paj hlwb thiab txo qis kev puas tsuaj, kev txhaj tshuaj tuaj yeem pab txhim kho cov kev mob tshwm sim ntawm cov neeg mob uas muaj kab mob neurological.
Vim muaj kev sib raug zoo ntawm MOTS c thiab cov txheej txheem kev laus, uas tuaj yeem tswj cov kev laus phenotype ntawm cov hlwb, nws yuav muaj txiaj ntsig zoo hauv kev kho cov kab mob laus. Los ntawm kev ua kom muaj kev tiv thaiv kev tiv thaiv - cov noob laus thiab cov kev taw qhia, nws tuaj yeem pab ncua kev laus thiab txhim kho kev noj qab haus huv ntawm cov neeg laus.
R&D Kev Sib Tw
Teeb meem kev ruaj ntseg
Raws li cov tshuaj peptide luv luv, MOTS c muaj kev ruaj ntseg tsis zoo thiab yooj yim degraded los ntawm enzymes hauv lub cev, uas cuam tshuam rau nws cov bioavailability thiab kev ua tau zoo. Nyob rau hauv txoj kev loj hlob ntawm kev txhaj tshuaj, nws yog ib qho tsim nyog yuav tau hais txog qhov teeb meem kev ruaj ntseg ntawm MOTS c kom ntseeg tau tias nws muaj txiaj ntsig zoo thiab lub sijhawm ua haujlwm hauv lub cev.
Txoj kev tswj hwm thiab kev xaiv ntau npaum li cas
Yuav ua li cas txhawm rau txhim kho txoj kev tswj hwm, txhim kho bioavailability, thiab txo cov kev mob tshwm sim yog ib qho teeb meem tseem ceeb uas yuav tsum tau hais txog hauv txoj kev loj hlob ntawm MOTS c txhaj tshuaj. Cov txheej txheem kev tswj hwm sib txawv (xws li kev txhaj tshuaj intravenous, txhaj tshuaj subcutaneous, thiab lwm yam) tuaj yeem cuam tshuam rau kev nqus, kev faib tawm, thiab cov metabolism hauv cov tshuaj, yog li hauv - kev tshawb fawb tob yog xav tau los xaiv txoj kev tswj hwm zoo tshaj plaws. Nyob rau tib lub sijhawm, nws yog ib qho tsim nyog los txiav txim siab qhov ntau npaum li cas kom ua tiav cov txiaj ntsig zoo tshaj plaws thiab kev nyab xeeb.
Kev ntsuas kev nyab xeeb
Ua ntej qhiaMOTS-c txhajNyob rau hauv kev xyaum kho mob, yuav tsum muaj kev ntsuam xyuas kev nyab xeeb. Qhov no suav nrog kev tshawb fawb txog toxicity, immunogenicity, toxicity reproductive, thiab lwm yam ntawm cov tshuaj kom ntseeg tau tias lawv muaj kev nyab xeeb hauv tib neeg lub cev.
MOTS-c txhaj tshuaj sawv cev rau kev nce qib hauv cov tshuaj mitochondrial, muab ntau txoj hauv kev los kho cov kab mob metabolic, kev laus- kab mob ntsig txog, thiab txhim kho lub cev kev ua haujlwm. Nws cov txheej txheem tshwj xeeb ntawm kev ua haujlwm-bridgeging mitochondrial thiab nuclear signaling- tso nws ua qhov muaj peev xwm ua ntej- hauv - kev kho hauv chav kawm.
Txawm hais tias cov ntaub ntawv kho mob thaum ntxov tau cog lus tseg, yuav tsum muaj kev sim loj dua kom paub meej tias ntev ntev - kev ua tau zoo thiab kev nyab xeeb. Cov kev sib tw suav nrog kev ua kom zoo tshaj plaws rau kev tso tawm kom ruaj khov, txo cov nqi, thiab nthuav tawm cov lus qhia tshaj li kev noj qab haus huv metabolic.
Raws li kev tshawb fawb txuas ntxiv mus, MOTS-c tuaj yeem hloov kho cov tswv yim kho mob rau kev txhim kho tib neeg kev noj qab haus huv, muab kev cia siab rau ntau lab tus neeg raug kev txom nyem los ntawm cov kab mob ntev txuas rau mitochondrial dysfunction.
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