Motc 10 mg

▎ Motc Structure

Source: PubChem

Sequence: MRWQEMGYIFYPRKLR Cov roj formula: C101H152N28O22S2 Molecular Luj: 2174.6g/mol CAS Nr .: 1627580-64-6 PubChem CID: 146675088 Synonyms: UNII-A5CV6JFB78

▎ Motc Kev Tshawb Fawb

Kev tshawb fawb keeb kwm ntawm Motc yog dab tsi?

Lub mitochondrion yog qhov chaw tseem ceeb rau lub zog metabolism hauv cov hlwb. Tau ntev, cov kws tshawb fawb tau tshawb fawb ntau thiab tob txog cov qauv thiab kev ua haujlwm ntawm mitochondria. Hauv cov txheej txheem no, nws tau maj mam lees paub tias mitochondria tsis tsuas yog ua lub luag haujlwm tseem ceeb hauv kev tsim hluav taws xob tab sis kuj tseem tuaj yeem koom nrog lwm cov txheej txheem physiological ntawm cov hlwb los ntawm qee yam tsis paub txog.

Nrog kev nce qib ntawm kev tshawb fawb thev naus laus zis, tshwj xeeb tshaj yog kev txhim kho ntawm genomics thiab proteomics technologies, nws tau dhau los ua kom pom cov mitochondria tshiab txog cov molecules. Motc (mitochondrial qhib nyeem ncej ntawm 12S rRNA-c) yog mitochondria-derived peptide encoded los ntawm 12S rRNA cheeb tsam ntawm mitochondrial genome ^[1].

Los ntawm kev txheeb xyuas qhov tob ntawm mitochondrial genome, cov kws tshawb fawb tau tshawb pom qee qhov qhib kev nyeem ntawv me me (sORFs), uas tuaj yeem nkag mus rau qee qhov peptides nrog cov haujlwm tshwj xeeb. Tom qab tshawb nrhiav thiab tshawb xyuas ntxiv, Motc tau txheeb xyuas. Kev tshawb fawb tau pom tias Motc tau qhia ntau yam ntaub so ntswg hauv tib neeg thiab tsiaj txhu. Nws feem ntau ua rau cov leeg pob txha los ntawm cov hlab ntsha, ua rau kom nce thiab siv cov piam thaj, yog li txhim kho cov tshuaj insulin thiab tswj cov metabolism hauv kev sib npaug ^[2].

Nrog rau kev tshawb fawb tob zuj zus, nws tau pom tias kev hloov pauv hauv kev qhia ntawm Motc muaj feem cuam tshuam nrog kev tshwm sim thiab kev loj hlob ntawm kev laus thiab cov kab mob uas muaj hnub nyoog. Piv txwv li, theem ntawm Motc hauv plasma txo qis nrog hnub nyoog (Zheng Y, 2013). Tib lub sijhawm, Motc tau raug pov thawj tias muaj txiaj ntsig zoo rau cov kab mob muaj hnub nyoog, suav nrog cov metabolism, kab mob plawv, osteoporosis, postmenopausal rog, thiab Alzheimer's disease ^[3].

Lub mechanism ntawm kev txiav txim ntawm Motc yog dab tsi?

Regulating gene expression: 

Motc tuaj yeem siv nws lub cev ua haujlwm los ntawm kev tswj cov noob qhia. Piv txwv li, nws tuaj yeem tswj cov kev qhia ntawm cov noob xws li GLUT4, STAT3, thiab IL-10. Motc feem ntau siv nws cov txiaj ntsig los ntawm kev ua kom lub AICAR-AMPK teeb liab txoj hauv kev thiab cuam tshuam lub voj voog folate-methionine hauv hlwb ^[4].

Txhim kho insulin tsis kam: 

Motc tuaj yeem txo cov tshuaj insulin thiab tiv thaiv hom 2 metabolism. Nws cov txheej txheem ntawm kev ua haujlwm yuav cuam tshuam nrog inhibition ntawm myostatin. Cov kev tshawb fawb tau pom tias qib plasma Motc cuam tshuam tsis zoo nrog cov qib myostatin hauv tib neeg lub cev. Motc tuaj yeem txhim kho insulin rhiab heev los ntawm inhibiting cov haujlwm ntawm cov khoom siv hluav taws xob sab saud FOXO1 thiab txo cov qib myostatin ^[5].

Txhawb cov leeg sib txawv: 

Hauv cov leeg nqaij, Motc cuam tshuam nrog STAT3 los ntawm kev sib koom ua ke SH2 binding motif hauv cheeb tsam YIFY, txo cov kev ua haujlwm ntawm STAT3, yog li txhim kho myotube tsim. Cov tsiaj qus-hom Motc peptide tuaj yeem nce myotube tsim ntawm tib neeg (LHCN-M2) thiab nas (C2C12) cov leeg nqaij progenitor thiab tiv thaiv cov leeg hlwb los ntawm kev txo cov myogenin staining induced los ntawm interleukin-6 (IL-6) ^[6].

Regulating mitochondrial muaj nuj nqi: 

Motc tuaj yeem tswj cov mitochondrial metabolism. Cov kev tshawb fawb tau pom tias kev kho cov kab mob mammalian nrog Motc tuaj yeem ua rau cov protein ntau ntawm mitochondrial biogenesis cov cim TFAM, COX4, thiab NRF1, tab sis ntws cytometry tsom xam pom tias tus naj npawb ntawm mitochondria txo qis tom qab Motc kho. Cov kev tshawb fawb ntxiv tau pom tias Motc tuaj yeem ua kom cov mitochondrial fusion thiab ua kom cov protein ntau ntawm ob GTPases, OPA1 thiab MFN2, uas yog qhov tseem ceeb rau kev sib xyaw ntawm cov tsiaj mitochondria. Inhibiting ob GTPases los yog khob MFN2 los ntawm siRNA yuav tshem tawm lub peev xwm ntawm Motc los txhawb GLUT4 translocation thiab qabzib uptake ^[7].

Motc yog lub hom phiaj kho mob rau ntau yam kabmob ntsig txog kev laus, suav nrog neurodegeneration, osteoporosis, kab mob plawv, atherosclerosis, sarcopenia, hom 2 metabolism mellitus, thiab rog.

Source: PubMed ^[8]

Dab tsi yog cov ntawv thov ntawm Motc?

Txhim kho cov kab mob uas muaj hnub nyoog

Kev sib raug zoo nrog kev laus: 

Motc yog ib qho mitochondria-derived peptide, thiab cov kev hloov hauv nws cov lus qhia yog ze ze rau qhov tshwm sim thiab kev loj hlob ntawm kev laus thiab cov kab mob uas muaj hnub nyoog. Raws li cov neeg muaj hnub nyoog, theem ntawm Motc txo. Cov kev tshawb fawb tau pom tias kev tawm dag zog muaj feem cuam tshuam rau kev qhia ntawm Motc, thiab Motc tuaj yeem kho qhov kev tiv thaiv kev laus ntawm kev tawm dag zog ^[3].

Metabolism: 

Motc tuaj yeem txhim kho lub cev cov piam thaj thiab lipid metabolism, txhawb kev ua haujlwm mitochondrial hauv cov hlwb, thiab txo qis cov kab mob ntev ntev. Rau cov neeg mob ntshav qab zib, qib ntawm Motc hauv plasma txo qis. Motc tuaj yeem tswj hwm cov metabolism hauv homeostasis los ntawm kev ua kom cov piam thaj nce ntxiv thiab txhim kho insulin rhiab heev, thiab nws muaj txiaj ntsig zoo rau kev tiv thaiv hom 2 metabolism ^[8].

Cov kab mob plawv: 

Kev kho mob plawv thiab kev ua haujlwm tsis zoo yog cov teeb meem ntawm cov metabolism, feem ntau ua rau mob plawv plawv. Motc tuaj yeem txhim kho vascular endothelial muaj nuj nqi thiab yog lub hom phiaj kho mob tshiab rau cov teeb meem ntawm cov hlab plawv ntawm cov metabolism. Cov kev tshawb fawb tau pom tias Motc tuaj yeem kho myocardial mitochondrial kev puas tsuaj hauv cov nas mob ntshav qab zib thiab tiv thaiv lub plawv systolic thiab diastolic zog ^[9].

Osteoporosis: Motc tuaj yeem txhawb kev loj hlob, kev sib txawv, thiab kev ntxhib los mos ntawm osteoblasts, inhibit osteoclast genesis, thiab tswj cov pob txha metabolism thiab kho pob txha. Kev tawm dag zog tuaj yeem txhim kho qhov kev qhia ntawm Motc, tab sis cov txheej txheem tshwj xeeb los ntawm kev tawm dag zog tswj Motc hauv cov pob txha tseem tsis meej ^[10].

Lwm yam kab mob

Pulmonary fibrosis: 

Pulmonary fibrosis yog ib yam kab mob ntsws loj uas muaj qhov tsis zoo, thiab nws cov etiology thiab pathogenesis tseem tsis meej. Lub mitochondrial qhib kev nyeem ntawv ntawm 12S rRNA-c (Motc) yog peptide encoded los ntawm mitochondrial genome, uas muaj txiaj ntsig zoo rau cov piam thaj thiab lipid metabolism, cellular thiab mitochondrial homeostasis, thiab txo qis ntawm cov kab mob inflammatory teb, thiab tej zaum yuav yog ib qho kev tawm dag zog mimetic. Qhov kev tshuaj xyuas no yog txhawm rau txheeb xyuas cov ntaub ntawv uas twb muaj lawm txog lub luag haujlwm ntawm Motc hauv kev txhim kho txoj kev loj hlob ntawm pulmonary fibrosis thiab txheeb xyuas cov hom phiaj kho mob tshwj xeeb rau cov tswv yim kho mob yav tom ntej ^[11].

Duchenne muscular dystrophy: 

Motc yog ib qho mitochondria-derived bioactive peptide nrog rau cov leeg nqaij-tshuaj, uas tuaj yeem ua rau cov leeg glycolytic flux thiab lub zog tsim muaj peev xwm ntawm cov leeg nqaij dystrophic hauv vitro thiab hauv vivo, yog li txhim kho kev nce thiab kev ua haujlwm ntawm phosphonodiamidite morpholino oligomers (PMOice). Kev rov ua haujlwm ntev ntev ntawm Motc thiab PMO tuaj yeem ua rau muaj kev qhia txog kev kho mob qib dystrophin hauv cov leeg nqaij, txhim kho cov leeg nqaij thiab pathology ntawm mdx nas, thiab tsis muaj qhov pom tseeb toxicity ^[12].

Obesity thiab nqaij atrophy: 

Kev rog rog thiab hom 2 metabolism yog cov kab mob metabolic feem ntau cuam tshuam nrog sarcopenia thiab cov leeg tsis ua haujlwm. Motc, raws li ib tug systemic hormone, koom nyob rau hauv metabolic homeostasis. Cov kev tshawb fawb tau pom tias qib plasma Motc cuam tshuam tsis zoo nrog cov qib myostatin hauv tib neeg lub cev. Motc tuaj yeem tiv thaiv palmitic acid-induced atrophy ntawm txawv C2C12 myotubes thiab txo cov qib myostatin hauv cov ntshav ntawm cov nas rog rog. Los ntawm inhibiting myostatin, Motc yuav yog ib qho kev kho mob rau cov leeg pob txha atrophy tshwm sim los ntawm insulin tsis kam thiab lwm yam nqaij atrophy phenotypes nrog rau sarcopenia ^[5].

Kev pheej hmoo ntawm cov kab mob metabolic hauv cov neeg muaj mob qog noj ntshav mis: 

Cov poj niam uas tau txais kev kho mob qog noj ntshav mis yog qhov muaj feem ntau ntawm cov kab mob plawv, cov metabolism, thiab rog, thiab kev tawm dag zog tuaj yeem txo cov kev mob tshwm sim no. Motc muaj kev tawm dag zog ua si thiab muaj txiaj ntsig zoo rau cov metabolism thiab muaj peev xwm ua haujlwm. Cov kev tshawb fawb tau pom tias 16-lub lim tiam aerobic thiab tiv thaiv kev tawm dag zog tuaj yeem ua rau nce qib Motc hauv cov neeg mob qog noj ntshav tsis yog neeg Mev, tab sis tsis muaj txiaj ntsig zoo rau cov neeg mob qog noj ntshav hauv Hispanic. Qhov nce hauv qib Motc raug ntxias los ntawm kev tawm dag zog hauv cov neeg mob qog noj ntshav uas tsis yog Hispanic muaj sia nyob yuav cuam tshuam nrog kev txhim kho ntawm insulin rhiab heev, yog li txo qhov kev pheej hmoo ntawm comorbidities ^[13].

Hauv kev xaus, raws li 16-amino acid polypeptide encoded los ntawm mitochondrial genome, Motc plays lub luag haujlwm tseem ceeb hauv lub cev cov txheej txheem metabolic, tiv thaiv kev ntxhov siab, thiab kev tiv thaiv kab mob thiab kev kho mob. Nws tuaj yeem txhim kho homeostasis ntawm qabzib thiab lipid metabolism, txhim kho insulin rhiab heev, thiab inhibit qhov kev qhia ntawm myostatin, zoo txo ​​cov metabolism hauv hom 2, rog rog, thiab cov leeg nqaij atrophy. Nyob rau tib lub sijhawm, los ntawm kev tswj hwm mitochondrial biogenesis thiab fusion, Motc txhim kho lub cell lub peev xwm antioxidant thiab inhibits cov lus teb inflammatory, qhia txog kev kho mob rau cov kab mob ntev xws li kab mob plawv, osteoporosis, thiab pulmonary fibrosis. Qhov tseem ceeb tshaj plaws, raws li tus neeg nruab nrab tseem ceeb ntawm kev sib txuas lus mitochondria-nucleus, Motc tuaj yeem simulate cov teebmeem ntawm kev tawm dag zog thiab ncua kev laus. Nws qib tsis zoo cuam tshuam nrog cov kab mob muaj hnub nyoog, thiab exogenous supplementation tuaj yeem thim rov qab cov kab mob metabolic thiab inhibit viral replication. Nws yog lub npe hu ua 'mitochondrial hormone'.

Hais Txog Tus Sau

Cov ntaub ntawv hais saum toj no yog txhua yam tshawb fawb, kho thiab sau los ntawm Cocer Peptides.

Scientific Journal Author

Dieli-Conwright CM yog tus kws tshawb fawb uas muaj kev cuam tshuam tseem ceeb hauv kev sib koom tes ntawm oncology thiab kev tawm dag zog kev tshawb fawb. Tam sim no nws tau ua tus kws tshaj lij ntawm cov tshuaj hauv Harvard Medical School thiab Dana-Farber Cancer Institute thiab tuav ib tus kws qhia ntawv hauv lub Department of Nutrition ntawm Harvard TH Chan Tsev Kawm Ntawv Kev Noj Qab Haus Huv. Dr. Dieli-Conwright txoj kev tshawb fawb tsom mus rau kev tshawb nrhiav qhov cuam tshuam ntawm kev tawm dag zog rau cov neeg mob qog noj ntshav, tshwj xeeb tshaj yog li cas kev tawm dag zog tuaj yeem txhim kho lub cev muaj zog, kev noj qab haus huv ntawm pob txha, thiab lub neej zoo ntawm cov neeg mob qog noj ntshav. Nws keeb kwm kev kawm suav nrog ntau yam xws li biology, kinesiology, kev noj qab haus huv pej xeem, thiab biokinesiology. Nws kawm tiav nws cov kev kawm hauv cov tsev kawm ntawv xws li California State University, Northridge, thiab University of Southern California thiab ua tiav nws cov kev tshawb fawb tom qab kawm tiav ntawm Lub Nroog Hope National Medical Center. Dr. Dieli-Conwright cov kev tshawb fawb tau txais txiaj ntsig tau tshaj tawm hauv ntau cov ntawv xov xwm kev kawm, thiab nws txoj haujlwm muaj ntau yam kev qhuab qhia xws li kev noj qab haus huv rau pej xeem, khoom noj khoom haus, kab mob plawv, thiab mob plawv, muab pov thawj tseem ceeb rau kev kho mob thiab kev noj qab haus huv ntawm cov neeg mob qog noj ntshav. Dieli-Conwright CM tau teev nyob rau hauv qhov kev siv ntawm cov ntaub ntawv pov thawj [13].

▎ Cov Lus Qhia Tseem Ceeb

[1] Zheng Y, Wei Z, Wang T. Motc: Kev cog lus mitochondrial-derived peptide rau kev siv tshuaj kho[J]. Frontiers hauv Endocrinology, 2023,14.DOI:10.3389/fendo.2023.1120533.

[2] Boyu Y. Kev tawm dag zog thiab Motc nce mitochondrial-derived peptide Motc qhia thiab txhim kho insulin tsis kam ntawm AMPK/PGC-1α txoj hauv kev [D]. Medical University, 2019.10.27652/d.cnki.gzyku.2019.001531.

[3] Mohtashami Z, Singh MK, Salimiaghdam N, et al. Motc, Feem Ntau Tsis ntev los no Mitochondrial Derived Peptide hauv Tib Neeg Kev Laus thiab Kab Mob Hnub Nyoog [J]. International Journal of Molecular Sciences, 2022,23(19).DOI:10.3390/ijms231911991.

[4] Gao Y, Wei X, Wei P, et al. Motc Functionally Prevents Metabolic Disorders [J]. Metabolites, 2023,13(1).DOI:10.3390/metabo13010125.

[5] Kumagai H, Coelho AR, Wan J, et al. Motc txo myostatin thiab nqaij atrophy signaling [J]. American Journal of Physiology-Endocrinology thiab Metabolism, 2021,320(4):E680-E690.DOI:10.1152/ajpendo.00275.2020.

[6] Garcia Benlloch S, Francisco RR, Rafael Blesa J, et al. Motc txhawb cov leeg sib txawv hauv vitro[J]. Peptides, 2022,155.DOI:10.1016/j.peptides.2022.170840.

[7] Bhullar KS, Shang N, Kerek E, et al. Mitofusion yog xav tau rau Motc induced GLUT4 translocation [J]. Scientific Reports, 2021,11(1).DOI:10.1038/s41598-021-93735-2.

[8] Kong BS, Lee C, Cho YM. Mitochondrial-Encoded Peptide Motc, Metabolism, and Aging-Related Diseases[J]. Metabolism & Metabolism Journal, 2023,47(3):315-324.DOI:10.4093/dmj.2022.0333.

[9] Wang M, Wang G, Pang X, et al. Motc kho myocardial kev puas tsuaj los ntawm inhibiting CCN1 / ERK1 / 2 / EGR1 txoj hauv kev hauv cov nas mob ntshav qab zib [J]. Frontiers in Nutrition, 2023,9.DOI:10.3389/fnut.2022.1060684.

[10] Yi X, Hu G, Yang Y, et al. Lub luag haujlwm ntawm Motc hauv kev tswj cov pob txha metabolism [J]. Frontiers hauv Physiology, 2023,14.DOI:10.3389/fphys.2023.1149120.

[11] Zhang Z, Chen D, Du K, et al. Motc: Lub peev xwm tiv thaiv pulmonary fibrosis tau muab los ntawm mitochondria [J]. Mitochondrion, 2023, 71: 76-82.DOI: 10.1016/j.mito.2023.06.002.

[12] Ran N, Lin C, Leng L, et al. Motc txhawb nqa phosphorodiamidate morpholino oligomer uptake thiab ua tau zoo hauv cov nas dystrophic [J]. Embo Molecular Medicine, 2021,13(2).DOI:10.15252/emmm.202012993.

[13] Dieli-Conwright CM, Nathalie S, KNM, et al. Cov txiaj ntsig ntawm aerobic thiab kev tawm dag zog ua haujlwm ntawm mitochondrial peptide MOTSc hauv Mev thiab tsis yog Hispanic cov neeg muaj mob qog noj ntshav [J]. Cancer Research, 2021,81(13).

Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.  

Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.