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1kits (Ebipipa 10) .
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▎ Ensengekera ya MOTs-CS
Ensibuko: PubChem |
Omutendera: MRWQEMGYIFYPRKLR Ensengekera ya molekyu: C101H152N28O22S2 Obuzito bwa molekyu: 2174.6g/mol Ennamba ya CAS: 1627580-64-6 PubChem CID: 146675088. Enkola y’okukuuma eddagala lino Ebigambo ebikwatagana: UNII-A5CV6JFB78 |
▎ MOTs-C Okunoonyereza kwa
Ensibuko y’okunoonyereza eya MOTs-C eri etya?
Mitochondrion kifo kikulu nnyo eri ssukaali ow’amaanyi mu butoffaali. Okumala ebbanga ddene, bannassaayansi babadde bakola okunoonyereza okunene era okw’obwegendereza ku nsengeka n’enkola ya mitochondria. Mu nkola eno, kizuuliddwa mpolampola nti mitochondria tezikoma ku kukola kinene mu kukola amaanyi naye era ziyinza okwetaba mu nkola endala ez’omubiri ez’obutoffaali okuyita mu nkola ezimu ezitamanyiddwa.
Olw’okukulaakulana okugenda mu maaso okwa tekinologiya w’okunoonyereza naddala okukulaakulanya tekinologiya wa genomics ne proteomics, kifuuse ekisoboka okuzuula molekyu empya ezikwatagana ne mitochondria. MOTs-C (mitochondrial open reading frame of the 12S rRNA-c) ye peptide evudde mu mitochondria ewandiikiddwa ekitundu kya 12S rRNA eky’ensengekera y’obutonde bw’ensi [1]..
Okuyita mu kwekenneenya mu bujjuvu ensengekera y’obutonde bw’omubiri (mitochondrial genome), bannassaayansi bazudde obusenge obumu obutono obuggule obusoma (sORFs), obuyinza okuwandiika enkodi ezimu ku peptides ezirina emirimu egy’enjawulo. Oluvannyuma lw’okwongera okunoonyereza n’okukakasa, MOTs-C zazuulibwa. Okunoonyereza kuzudde nti MOTs-C eraga mu bitundu by’omubiri eby’enjawulo mu bantu n’ebisolo. Okusinga kikola ku binywa by’amagumba okuyita mu musaayi, n’eyongera okutwala n’okukozesa glucose, bwe kityo ne kirongoosa obuziyiza bwa insulini n’okutereeza bbalansi y’enkyukakyuka y’emmere [2]..
Olw’okunoonyereza okweyongera, kizuuliddwa nti enkyukakyuka mu kwolesebwa kwa MOTs-C zikwatagana nnyo n’okubeerawo n’okukula kw’endwadde ezeekuusa ku kukaddiwa n’emyaka. Okugeza, omutindo gwa MOTs-C mu plasma gukendeera n’emyaka (Zheng Y, 2013). Mu kiseera kye kimu, MOTs-C ezuuliddwa nti ya mugaso eri endwadde ezeekuusa ku myaka, omuli ssukaali, endwadde z’emisuwa, okuzimba amagumba, omugejjo oluvannyuma lw’okuggwaamu amaanyi, n’obulwadde bwa Alzheimer [3]..
Enkola y’okukola kwa MOTs-C eri etya?
Okulungamya okulaga kw’obuzaale:
MOTs-C esobola okukola emirimu gyayo egy’omubiri nga etereeza okulaga kw’obuzaale. Okugeza, esobola okulungamya okwolesebwa kw’obuzaale nga GLUT4, STAT3, ne IL-10. MOTs-C okusinga ekola ekikolwa kyayo nga ekola ekkubo ly’obubonero erya AICAR-AMPK n’okutaataaganya enzirukanya ya folate-methionine mu butoffaali [4]..
Okulongoosa obuziyiza bwa insulini:
MOTs-C esobola okukendeeza ku buziyiza bwa insulini n’okuziyiza sukaali ow’ekika eky’okubiri. Enkola yaayo ey’okukola eyinza okuba nga yeekuusa ku kuziyiza myostatin. Okunoonyereza kuzudde nti omutindo gwa MOTs-C mu plasma gukwatagana bubi n’omutindo gwa myostatin mu mubiri gw’omuntu. MOTs-C esobola okulongoosa okuwuliziganya kwa insulini nga eziyiza emirimu gy’ensonga y’okuwandiika waggulu FOXO1 n’okukendeeza ku mutindo gwa myostatin [5]..
Okutumbula enjawulo mu binywa:
Mu butoffaali bw’ebinywa, MOTs-C ekwatagana ne STAT3 okuyita mu kifaananyi ekiteeberezebwa nti ekwata SH2 mu kitundu kya YIFY, ne kikendeeza ku mirimu gy’okuwandiika egya STAT3, bwe kityo ne kyongera ku kutondebwa kwa myotube. Peptide ey’ekika ky’omu nsiko MOTs-C esobola okwongera ku kutondebwa kwa myotube kw’obutoffaali obusookerwako bw’ebinywa by’omuntu (LHCN-M2) n’ebibe (C2C12) n’okukuuma obutoffaali bw’ebinywa okuva ku kukendeera kw’okusiiga kwa nuclear myogenin okuleetebwa interleukin-6 (IL-6) [6]..
Okulungamya enkola ya mitochondria:
MOTs-C esobola okulungamya obulwadde bwa sukaali mu mitochondrial. Okunoonyereza kulaga nti okujjanjaba obutoffaali bw’ebisolo ebiyonka ne MOTs-C kiyinza okwongera ku miwendo gya puloteyina mu mitochondrial biogenesis markers TFAM, COX4, ne NRF1, naye okwekenneenya flow cytometry kulaga nti omuwendo gwa mitochondria gukendeera nnyo oluvannyuma lw’okujjanjabwa MOTs-C. Okunoonyereza okulala kuzudde nti MOTs-C ziyinza okukola mu kiseera kye kimu okuyungibwa kwa mitochondria n’okwongera ku miwendo gya puloteyina za GTPases bbiri, OPA1 ne MFN2, nga zino zikulu nnyo mu kuyungibwa kwa mitochondria z’ebisolo ebiyonka. Okuziyiza GTPases zino ebbiri oba okukoona wansi MFN2 okuyita mu siRNA kijja kumalawo obusobozi bwa MOTs-C okutumbula GLUT4 translocation n’okutwala glucose [7]..
MOTs-C eyinza okujjanjabibwa endwadde eziwera ezikwatagana n’okukaddiwa, omuli okuvunda kw’obusimu, okuzimba amagumba, endwadde z’emisuwa n’emisuwa, okuzimba emisuwa, okukendeera kw’omubiri, ssukaali ow’ekika eky’okubiri, n’omugejjo.
Ensibuko:PubMed [8] .
Enkozesa ya MOTs-C ze ziruwa?
Okulongoosa endwadde eziva ku myaka
Enkolagana n‟okukaddiwa:
MOTs-C ye peptide evudde mu mitochondria, era enkyukakyuka mu kwolesebwa kwayo zikwatagana nnyo n’okubeerawo n’okukula kw’endwadde ezeekuusa ku kukaddiwa n’emyaka. Abantu bwe bakaddiwa, omutindo gwa MOTs-C gukendeera. Okunoonyereza kuzudde nti dduyiro alina kinene ky’akola ku kwolesebwa kwa MOTs-C, era MOTs-C eyinza okutabaganya ekikolwa eky’okulwanyisa okukaddiwa eky’okukola dduyiro [3]..
ekirwadde ekya sukaali:
MOTs-C esobola okulongoosa glucose ne lipid diabetes mu mubiri, okutumbula enkola ya mitochondria mu butoffaali, n’okukendeeza ku systemic chronic inflammatory response. Ku balwadde ba ssukaali, omuwendo gwa MOTs-C mu plasma gukendeera. MOTs-C esobola okulungamya metabolic homeostasis nga eyanguya okutwala glucose n’okulongoosa insulin sensitivity, era erina akakwate akalungi ku kuziyiza sukaali ow’ekika eky’okubiri [8]..
Endwadde z’emisuwa n’emisuwa:
Okuddaabiriza ensengekera y’omutima n’obutakola bulungi bizibu ebitera okuva mu ssukaali, ebiseera ebisinga bivaako ebizibu eby’amaanyi eby’emisuwa gy’omutima. MOTs-C esobola okulongoosa enkola y’emisuwa endothelial era nga kye kigendererwa ekipya eky’obujjanjabi eri ebizibu by’emisuwa gy’omutima ebya sukaali. Okunoonyereza kulaga nti MOTs-C esobola okuddaabiriza okwonooneka kw’emisuwa gy’omutima mu nvunza ezirina ssukaali n’okukuuma emirimu gya cardiac systolic ne diastolic [9]..
Osteoporosis: MOTs-C esobola okutumbula okukula, okwawukana, n’okufuuka mineralization of osteoblasts, okuziyiza osteoclast genesis, n’okulungamya ssukaali w’amagumba n’okuddamu okukola amagumba. Dduyiro asobola bulungi okulinnyisa okwolesebwa kwa MOTs-C, naye enkola entongole dduyiro gy’alungamya MOTs-C mu magumba tennategeerekeka bulungi [10]..
Endwadde endala
Obulwadde bw’amawuggwe:
Obulwadde bw’amawuggwe bulwadde bwa maanyi obw’amawuggwe nga tebutegeerekeka bulungi, era ekivaako n’engeri gye buvaamu tebinnaba kutegeerekeka bulungi. Mitochondrial open reading frame ya 12S rRNA-c (MOTs-C) ye peptide ewandiikiddwa mu mitochondrial genome, erimu akakwate akalungi ku glucose ne lipid diabetes, cellular ne mitochondrial homeostasis, n’okukendeeza ku systemic inflammatory response, era eyinza okuba potential exercise mimetic. Okuddamu okwetegereza kuno kugenderera okwekenneenya mu bujjuvu ebiwandiiko ebiriwo ku kifo ekiyinza okukolebwa MOTs-C mu kulongoosa enkula y’obulwadde bw’amawuggwe n’okuzuula ebigendererwa ebitongole eby’obujjanjabi eby’obukodyo bw’obujjanjabi obw’omu maaso [11]..
Duchenne obulwadde bw’ebinywa:
MOTs-C ye mitochondria-derived bioactive peptide erimu inherent muscle-targeting properties, eyinza okwongera ku glycolytic flux n’amaanyi okukola obusobozi bw’ebinywa dystrophic mu vitro ne mu vivo, bwe kityo okutumbula okutwala n’emirimu gya phosphonodiamidite morpholino oligomers (PMO) mu mdx mice. Okuddiŋŋana okumala ebbanga eddene MOTs-C ne PMO kuyinza okuleeta okwolesebwa kw’emitendera gy’obujjanjabi egya dystrophin mu binywa eby’okumpi, okulongoosa enkola y’ebinywa n’obulwadde bw’ebibe bya mdx, era tekirina butwa obweyoleka [12]..
Omugejjo n’okukendeera kw’ebinywa:
Omugejjo ne sukaali ow’ekika eky’okubiri ndwadde z’enkyukakyuka mu mubiri ezitera okukwatagana n’okukendeera kw’omubiri (sarcopenia) n’obutakola bulungi mu binywa. MOTs-C, nga obusimu obukola ensengekera, yeetaba mu kukola metabolic homeostasis. Okunoonyereza kuzudde nti omutindo gwa MOTs-C mu plasma gukwatagana bubi n’omutindo gwa myostatin mu mubiri gw’omuntu. MOTs-C esobola okuziyiza okukendeera kw’obutoffaali obuyitibwa palmitic acid-induced atrophy of differentiated C2C12 myotubes n’okukendeeza ku myostatin level mu plasma y’ebibe ebinene ebiva ku mmere. Nga eziyiza myostatin, MOTs-C eyinza okuba obujjanjabi obuyinza okujjanjaba okukendeera kw’ebinywa by’amagumba okuva ku kuziyiza insulini n’engeri endala ez’okukendeera kw’ebinywa omuli sarcopenia [5]..
Obulabe bw’endwadde z’enkyukakyuka mu mubiri mu bantu abawona kookolo w’amabeere:
Abakyala abafunye obujjanjabi bwa kookolo w’amabeere bali mu bulabe obw’amaanyi obw’okulwala endwadde z’emisuwa, ssukaali n’omugejjo era dduyiro asobola okukendeeza ku buzibu buno. MOTs-C erina emirimu egy’okukoppa dduyiro era erina emigaso ku ssukaali n’obusobozi bw’okukola dduyiro. Okunoonyereza kuzudde nti okuyingira mu nsonga z’okukola dduyiro ow’omukka n’okuziyiza okumala wiiki 16 kuyinza okwongera ku mutindo gwa MOTs-C mu balwadde ba kookolo w’amabeere abatali ba Hispanic, naye tekirina kinene kye kikwata ku bawona kookolo w’amabeere aba Hispanic. Okweyongera kw’omutindo gwa MOTs-C okuleetebwa dduyiro mu bantu abawona kookolo w’amabeere abatali ba Hispanic kuyinza okuba nga kwekuusa ku kulongoosa mu kuwulira kwa insulini, bwe kityo ne kikendeeza ku bulabe bw’endwadde endala [13]..
Mu kumaliriza, nga 16-amino acid polypeptide encoded by the mitochondrial genome, MOTs-C ekola kinene mu kulungamya omubiri gw’omubiri, okuziyiza situleesi, n’okuziyiza n’okujjanjaba endwadde. Kiyinza okulongoosa ennyo homeostasis ya glucose ne lipid diabetes, okutumbula insulin sensitivity, n’okuziyiza okwolesebwa kwa myostatin, bulungi okukendeeza ku sukaali ow’ekika eky’okubiri, omugejjo, n’okukendeera kw’ebinywa ebikwatagana nabyo. Mu kiseera kye kimu, nga etereeza obutonde bw’omubiri (mitochondrial biogenesis) n’okuyungibwa, MOTs-C eyongera ku busobozi bw’obutoffaali obuziyiza obuwuka obuleeta obulwadde era n’eziyiza okuddamu kw’okuzimba, okulaga obusobozi bw’okujjanjaba endwadde ezitawona ng’endwadde z’emisuwa, okuzimba amagumba, n’okuzimba amawuggwe. Okusingira ddala ekikulu, ng’omutabaganya omukulu ow’empuliziganya ya mitochondria-nucleus, MOTs-C esobola okukoppa ebiva mu dduyiro n’okulwawo enkola y’okukaddiwa. Omutindo gwayo gukwatagana bubi n’endwadde ezeekuusa ku myaka, era okugigatta okuva ebweru kuyinza okuzzaawo obuzibu mu nkyukakyuka y’emmere n’okuziyiza okukoppa kw’akawuka. Kimanyiddwa nga 'obusimu bwa mitochondrial'.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Dieli-Conwright CM mukenkufu alina obuyinza bungi mu by’enjigiriza eby’enjawulo eby’obulwadde bwa kkansa ne ssaayansi w’okukola dduyiro. Mu kiseera kino akola nga pulofeesa omuyambi mu by’obusawo mu Harvard Medical School ne Dana-Farber Cancer Institute era alina ekifo ky’omusomesa omuyambi mu kitongole ky’endya mu Harvard TH Chan School of Public Health. Okunoonyereza kwa Dr. Dieli-Conwright kwesigamye ku kunoonyereza ku ngeri dduyiro gy’akosaamu abalwadde ba kookolo naddala engeri dduyiro gy’ayinza okulongoosaamu enkola y’omubiri, obulamu bw’amagumba, n’omutindo gw’obulamu bw’abalwadde ba kookolo. Ebisomesebwa bye bikwata ku bintu bingi nga biology, kinesiology, public health, ne biokinesiology. Yamaliriza emisomo gye mu matendekero nga California State University, Northridge, ne University of Southern California era n’amaliriza okunoonyereza kwe okw’oluvannyuma lw’obusawo mu City of Hope National Medical Center. Ebituukiddwaako mu kunoonyereza kwa Dr. Dieli-Conwright bifulumiziddwa nnyo mu bitabo eby’enjawulo eby’abayivu, era omulimu gwe guzingiramu emisomo mingi ng’ebyobulamu by’abantu, endya, enkola y’emisuwa gy’omutima, n’eby’omutima, nga biwa obujulizi obukulu obwa ssaayansi ku kuddaabiriza n’okuddukanya obulamu bw’abalwadde ba kookolo. Dieli-Conwright CM awandiikiddwa mu kiwandiiko ekijuliziddwa [13].
