MOTS-c 40mg

▎ MOTS-c Ọdịdị

▎ MOTS-c Nnyocha

Kedu ihe ndabere nyocha nke MOTS-c?

Mitochondria, na-eje ozi dị ka 'ụlọ ike' nke mkpụrụ ndụ, na-arụ ọrụ dị mkpa n'ịkwado homeostasis cellular. Usoro nzikọrịta ozi n'etiti mitochondria na nucleus bụ ogologo oge nyocha nke sayensị. Mitochondria nwere genome nọọrọ onwe ya. Ewezuga mkpụrụ ndụ ihe nketa 37 nke ochie, nnyocha ndị na-adịbeghị anya ekpughere na mitochondrial DNA na-etinyekwa peptides dị mkpụmkpụ na-arụ ọrụ ndụ, otu n'ime ha bụ peptide MOTS-c sitere na mitochondrial, nke mpaghara mitochondrial 12S rRNA debere ya. Nchọpụta a na-agbasawanye ohere nke mkpụrụ ndụ ihe nketa mitochondrial nke ukwuu, na-enye echiche ọhụụ maka ịkọwapụta usoro ndu dị oke mkpa dị ka nkwurịta okwu mitochondrial-nuklear na usoro metabolic.

Ugbu a, ọgwụgwọ maka ọtụtụ ọrịa siri ike dị ka ọrịa shuga na ịba ọcha n'anya B na-eche nnukwu nsogbu ihu. Ọrụ MOTS-c pụtara ìhè na nhazi usoro metabolic nke anụ ahụ, dị ka ịkwalite glucose metabolism, na-egosi ikike ọ nwere n'ịgwọ ọrịa metabolic. Ọzọkwa, ọkwa MOTS-c na-adịghị mma nke a na-ahụ na usoro ọrịa dị iche iche emeela ka ndị nchọpụta nyochaa ọrụ ya na mmalite ọrịa, ọganihu, na ọgwụgwọ, na-achọ ụzọ ọhụrụ iji merie ọnọdụ ndị a na-adịghị agwụ agwụ.

Kedu usoro eji arụ ọrụ maka MOTS-c?

Ụzọ nrịbama metụtara Metabolism na-achịkwa

Na-eme ka ụzọ mgbaama AICAR-AMPK rụọ ọrụ: MOTS-c na-eme ka ụzọ akara AICAR-AMPK rụọ ọrụ site na imebi okirikiri folate-methionine intracellular. AMPK arụ ọrụ na-achịkwa metabolism ike cell, dị ka ịkwalite nnabata glucose na oxidation fatty acid. Na metabolism nke glucose, ọ na-abawanye ntụgharị nke GLUT4 na-ebu glucose na akpụkpọ ahụ, si otú ahụ na-eme ka ikike nnabata glucose dị n'ime cell, na-eme ka nguzogide insulin dịkwuo elu, na inye aka na mgbochi na ọgwụgwọ nke ọrịa metabolic dị ka ụdị ọrịa shuga 2 ^..

Mmetụta na ụzọ ndị ọzọ: E wezụga ụzọ AMPK, MOTS-c na-emekwa ihe na ụzọ AKT, ụzọ nrụgide oxidative, na ụzọ ndị metụtara mbufụt. Banyere ụzọ AKT, ọ nwere ike imetụta usoro cellular dị ka uto, mmụba, na nlanarị site na ịhazi ọrụ nke ụzọ ahụ. N'okporo ụzọ nrụgide oxidative, MOTS-C na-ebelata ọkwa nrụgide oxidative intracellular, na-ebelata mmepụta ụdị oxygen (ROS), ma na-echebe mkpụrụ ndụ site na mmebi oxidative. N'ụzọ ndị metụtara mbufụt, ọ na-ebelata ntọhapụ nke ndị mgbasa ozi na-egbuke egbuke ma na-ebelata nzaghachi mkpali. Dịka ọmụmaatụ, n'ụdị mgbu na-egbuke egbuke, MOTS-C na-ebelata mwepụta onye mgbasa ozi mkpali na mpi dorsal nke ọkpụkpụ azụ, si otú ahụ na-emeziwanye mgbaàmà mgbu ^[2]..

Ọnụọgụ 1 Ọrụ physiological bụ isi nke MOTS-C gụnyere ibelata nguzogide insulin, igbochi oke ibu, imeziwanye ọrụ akwara, ịkwalite metabolism nke ọkpụkpụ, ịkwalite usoro mgbochi ọrịa, na igbu oge ^[1].

Iwu nke okwu Gene

Usoro nkwuputa okwu Gene Nuklia: Mgbe mkpụrụ ndụ na-ezute nrụgide metabolic, dị ka mmachi glucose na nrụgide oxidative, MOTS-C na-atụgharị na nucleus ka ọ na-ahazi okwu mkpụrụ ndụ ihe nketa nuklia ozugbo, si otú ahụ na-akwalite homeostasis intracellular. Dịka ọmụmaatụ, MOTS-C na-agbanwe okwu nke mkpụrụ ndụ ihe nketa metụtara metabolism dị ka GLUT4, STAT3, na IL-10, na-emetụta usoro physiological gụnyere glucose metabolism na usoro mgbochi. Mmụba okwu GLUT4 na-eme ka nnabata glucose dị n'ọbara; STAT3 na-ekere òkè n'ịba ụba nke cell, dị iche iche, na usoro nchịkwa; IL-10, cytokine na-egbochi mkpali, na-ebelata nzaghachi mkpali mgbe a na-ebuli okwu ya elu ^[1,3].

Ịkwalite Metabolism Energy

Glycolysis kwalitere: N'ụdị ọrịa dị iche iche, dị ka ngụgụ ischemia-reperfusion mmerụ (LIRI) ụdị nke na-akpata site cardiopulmonary bypass (CPB), MOTS-c pretreatment na-eme ka glycolytic flux na pulmonary microvascular endothelial cell (PMVECs). Ọ na-ebelata mmerụ ahụ LIRI site na iweghachi homeostasis ume cell yana ibelata peroxidation lipid site na ịkwalite isi glycolytic enzyme PFKFB3. Nke a na-egosi na MOTS-c na-agbanwe ụzọ glycolytic iji nye ike zuru oke maka mkpụrụ ndụ nọ n'okpuru nrụgide, si otú a na-ejigide ọrụ cellular nkịtị ^[4].

Mmetụta Nchekwa Cellular

Mbelata nke mmebi Mitochondrial: N'ụdị pneumonitis radieshon (RP), MOTS-c belatara mmerụ ahụ anụ ahụ nku ume, mbufụt, na nrụgide oxidative mgbe ọ na-atụgharị alveolar epithelial cell apoptosis na mmebi mitochondrial. Usoro a na-agụnye ịbawanye ọkwa 2 (Nrf2) metụtara ihe nuklia E2 na ịkwalite ntụgharị nuklia ya. Nrf2 na-arụ ọrụ usoro antioxidant na mkpụrụ ndụ ihe nchebe cell, na-echekwa ọrụ mitochondrial. Nke a na-egosi na MOTS-c na-echebe anụ ahụ mebiri emebi site na ichekwa mitochondria na ibelata apoptosis ^[5].

Nchedo nke mkpụrụ ndụ ndị ọzọ: N'ọmụmụ ihe na Duchenne muscular dystrophy (DMD), MOTS-c nwere ihe ndị na-eme ka anụ ahụ dị n'ime. Ọ na-eme ka glycolytic flux na ike mmepụta ike na akwara dystrophic, na-enye aka n'ịrụ ọrụ muscle ka mma. Ọzọkwa, na ụdị mgbu na-egbuke egbuke, MOTS-c nke a na-elekọta ma ọ bụ n'akụkụ ya na-ebelata ihe mgbu na-egbu mgbu site na igbochi nzaghachi mkpali na hyperexcitability neuronal, na-enye mmetụta neuroprotective ^[2,6]..

Kedu ihe bụ ngwa MOTS-c?

Ọgwụgwọ Ọrịa Metabolic:

Imelite nguzogide insulin na igbochi ọrịa shuga: MOTS-c na-akwalite nguzogide insulin, nke dị oke mkpa maka igbochi ụdị ọrịa shuga 2. Nguzogide insulin bụ isi ihe na-ebute mmalite nke ọrịa shuga 2. MOTS-c nwere ike imeziwanye mmetụta insulin site na ịgbalite ụzọ akara AICAR-AMPK na ịhazi okirikiri folate-methionine intracellular. Nnyocha nke Gao Y na-egosi na ọ na-akwalite nnabata glucose n'ime akwara skeletal, dị ka imepe ụzọ nnabata glucose ọzọ na sel, si otú a na-ebelata ọkwa glucose ọbara ^[1]..

Na-achịkwa metabolism lipid na ịlụso oke ibu ọgụ: Banyere metabolism lipid, MOTS-c na-abawanye thermogenesis abụba agba aja aja ma na-akwalite agba aja aja na-acha ọcha. Abụba aja aja na-eri ike site na thermogenesis, ebe abụba na-acha ọcha na-egosi mgbanwe ike na-echekwa abụba ọcha ka ọ bụrụ abụba aja aja na-eri ike. Usoro a na-enyere ahụ aka ime mgbanwe na oyi na, nke ka mkpa, na-egbochi oke ibu na nsogbu metabolism lipid, na-enye nghọta ọhụrụ maka mgbochi na ọgwụgwọ oke ibu ^[1].

Mgbochi na ọgwụgwọ nke ọrịa metụtara akwara:

Ịkwalite Ịdịiche Muscle: Nnyocha ọmụmụ vitro na-egosi na ụdị anụ ọhịa MOTS-c peptide na-eme ka ọkpụkpụ myotubular dị na mmadụ (LHCN-M2) na òké (C2C12) mkpụrụ ndụ progenitor muscle, ebe Y8F mutant peptide enweghị mmetụta a. Nnyocha ndị ọzọ gosipụtara na MOTS-c na-eme ka myotubulogenesis na-emekọrịta ihe site na iso ndị IL-6 / Janus kinase / transducer transducer na activator nke transcript 3 (STAT3), si otú ahụ belata STAT3 transcriptional ọrụ ^[7].

Mgbochi nke Atrophy Muscle: Plasma MOTS-c ọkwa na-adịghị mma na ọkwa myostatin. MOTS-c na-egbochi palmitate-induced myotube atrophy na sel C2C12 dị iche iche ma na-ebelata ọkwa myostatin plasma na oke oke ibu na-ebute nri. Ọ na-egbochi atrophy anụ ahụ site na ịkwalite AKT phosphorylation, na-egbochi ọrụ FOXO1-ihe ntinye ederede nke myostatin na mkpụrụ ndụ akwara-atrophy ndị ọzọ-mgbe na-achịkwa mTORC2 na ọrụ PTEN na ịba ụba ọrụ CK2 iji kwụsị PTEN ^[8].

Mmetụta mgbochi ịka nká: Mgbanwe okwu MOTS-c nwere njikọ chiri anya na ịka nká, ọ na-egosipụtakwa ihe mgbochi ịka nká. A na-enweta nke a site n'ọtụtụ usoro, gụnyere imeziwanye glucose na metabolism lipid, na-eme ka ọrụ mitochondrial cellular dịkwuo elu, na ibelata mbufụt na-adịghị ala ala. Nnyocha nke Gao Y et al. na-egosi na metabolism ka mma na-enye mkpụrụ ndụ n'ụba ma kwụsie ike. Ịkwalite ọrụ mitochondrial yiri ịkwalite ụlọ ọrụ mmepụta ihe nke ume, ebe mbelata nzaghachi mkpali na-ebelata mmebi mkpali nke mkpụrụ ndụ ^[1].

Mmechi

Dị ka peptide sitere na mitochondrial, MOTS-c na-arụ ọrụ ụzọ mgbaàmà dị ka AMPK iji mezie glucose na lipid metabolism, na-akwalite mgbanwe abụba na-acha ọcha na agba aja aja, ma melite nguzogide insulin na oke ibu, na-enye ntụziaka ọgwụgwọ ọhụrụ maka nsogbu metabolic. Ọ na-eme ka ọdịiche osteoblast dịkwuo mma, na-egbochi nhazi osteoclast, na-edozi metabolism ọkpụkpụ, ma na-akwado nlekọta ahụike skeletal. Ọ na-achịkwa ọdịiche dị n'ahụ ahụ ma na-egbochi atrophy, na-ejide ikike itinye aka na nsogbu ndị metụtara akwara. MOTS-c na-egosiputa mkpakọrịta ndị metụtara mmega ahụ siri ike: mmega ahụ na-emezi nkwupụta ya, ọ na-edozikwa uru ahụike na-emega ahụ. MOTS-c na-ekerekwa òkè na igbu oge ịka nká na usoro ndị metụtara ya.

Banyere Onye dere ya

Ihe niile a kpọtụrụ aha n'elu bụ Cocer Peptides na-enyocha, dezie ma chịkọta ya.

Onye ode akwụkwọ akụkọ sayensị

Ning Ran bụ onye nyocha jikọtara ya na Carlson College of Veterinary Medicine na Mahadum Oregon State. Ọrụ agụmakwụkwọ ya gbasara usoro ihe ọmụmụ ihe omimi na ọgwụ ntụgharị, na-elekwasị anya na usoro ọgwụgwọ maka ọrịa neuromuscular. Ran ejikọtala ọtụtụ akwụkwọ n'akwụkwọ akụkọ ndị ọgbọ nyochara, na-enye aka na nghọta nke ntinye aka nke mkpụrụ ndụ na ụdị ọrịa. Mmasị nyocha ya gụnyere mmepe na itinye peptide-conjugated oligonucleotides, yana ịchọpụta ikike ọgwụgwọ nke peptides sitere na mitochondrial. Edepụtara Ning Ran na ntụnye aka nke ntụaka [6].

▎ Okwu ndị dị mkpa

[1] Gao Y, Wei X, Wei P, et al. MOTS-c na-egbochi arụrụ arụ nke metabolic. Metabolites 2023; 13(1).DOI: 10.3390/metabo13010125.

[2] Wang Z, Yang L, Xu L, Liao J, Lu P, Jiang J. Central na mpụta usoro nke MOTS-c attenuates mgbu hypersensitivity na a ụmụ oke ụdị mgbu mgbu. Nnyocha Neurological 2024; 46 (2): 165-177.DOI: 10.1080/01616412.2023.2258584.

[3] Benayoun BA, Lee C. MOTS-c: Mitochondrial-Encoded Regulator nke Nucleus. Bioessays 2019; 41 (9): e1900046.DOI: 10.1002/bies.201900046.

[4] Shen Z, Lu P, Jin W, et al. MOTS-c na-akwalite Glycolysis site na AMPK-HIF-1α-PFKFB3 Ụzọ maka mmerụ ahụ na-akpata CPB. Akwụkwọ akụkọ American of Respiratory Cell and Molecular Biology 2025. 10.1165/rcmb.2024-0533OC.

[5] Zhang Y, Huang J, Zhang Y, et al. Peptide nke Mitochondrial-enwetara MOTS-c na-ebelata Pneumonitis Radiation site na Nrf2-Dependent Mechanism. Antioxidants 2024; 13. https://api.semanticscholar.org/CorpusID:269876125.

[6] Ran N, Lin C, Leng L, et al. MOTS-c na-akwalite nnabata phosphorodiamidate morpholino oligomer na ịdị irè na ụmụ oke dystrophic. Embo Molecular Medicine 2021; 13(2): e12993.DOI: 10.15252/emmm.202012993.

[7] García-Benlloch S, Revert-Ros F, Blesa JR, Alis R. MOTS-c na-akwalite ọdịiche anụ ahụ na vitro. Peptides 2022; 155: 170840.DOI: 10.1016/j.peptides.2022.170840.

[8] Kumagai H, Coelho AR, Wan J, et al. MOTS-c na-ebelata myostatin na atrophy muscle. Akwụkwọ akụkọ American nke Physiology-Endocrinology na Metabolism 2021; 320(4): E680-E690.DOI: 10.1152/ajpendo.00275.2020.

Edemede na ozi ngwaahịa niile enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.  

Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadoghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.