01.
NMNHkwandisa i-NAD + yeselula kunye namanqanaba e-NADH. Abaphandi bathelekisa iziphumo ze-NMN kunye ne-NMNH ekwandiseni amanqanaba e-NAD + yeselula. Unyango nge-NMNH (100 μM) yonyuse amanqanaba e-NAD+ yeselula nge-5-fold kwiiseli ze-HepG2, ngelixa i-100 μM NMN yonyuka kancinane kuphela amanqanaba e-NAD+. Ukongeza kwiiseli ze-HepG2, abaphandi baphinde baqinisekisa ukuba i-NMNH iphucule i-NAD + kwiiseli ze-ES-2 kunye neeseli ze-3T3-L1, iiseli eziphuma kwi-ovary yabantu kunye neeseli ze-embryonic fibroblast-derived, ngokulandelanayo. Kwaye abaphandi bafumanisa ukuba i-NMNH yonyusa amanqanaba e-NAD + yeselula kwiiseli ze-786-O ngexesha kunye nokuxhomekeka koxinzelelo. Abaphandi balinganisa i-NADH ngokusebenzisa i-mass spectrometry kwaye bafumanisa ukuba amanqanaba e-NADH kwiiseli ze-HepG2 eziphathwa yi-NMNH zaziphezulu ngamaxesha angama-2.5 ngaphezu kweeseli ezingaphathwanga kunye ne-NMN, kwaye amanqanaba aphakamileyo e-NADH afunyenwe kwiiseli ze-786-O eziphathwa yi-NMNH. Siphinde safumanisa ukuba unyango lwe-340 mg / kg lwe-NMNH lwandise amanqanaba e-NADH kwisibindi segundane nge-3-fold, ngelixa i-340 mg / kg unyango lwe-NMN lwandisa amanqanaba e-NADH nge-1.7-fold.
Umfanekiso 1.2. I-NMNH yonyusa amanqanaba e-NAD+
Umfanekiso 3.4. I-NMNH yonyusa amanqanaba e-NMNH
I-02NMNH inqanda i-glycolysis kunye nomjikelezo we-TCA. Ukuqokelela kwe-NADH kunciphisa i-glycolysis kunye nomjikelezo we-TCA. Ukuphonononga impendulo ye-metabolic yeeseli kunyango lwe-NMNH, abaphandi benza uhlalutyo lwe-metabolomic
NMNH-kunye neeseli eziphathwe nge-NMN. Kwafunyaniswa ukuba unyango lwe-NMNH aluzange lunciphise kuphela amanqanaba e-glycolysis intermediates, kodwa lwanciphisa amanqanaba e-TCA cycle intermediates. Ezi ziphumo zibonisa ukuba ukuqokelela kwe-NADH eveliswe yi-NMNH inqanda i-cell glycolysis kunye nomjikelezo we-TCA.
Umzobo 5. Ukunciphisa i-glycolysis kunye ne-TCA cycle intermediates
Umzobo 6. Uhlalutyo lwe-Metabolomics
03.
NMNHinqanda ukukhula kweeseli Abaphandi bahlolisise umphumo we-NMNH ekukhuleni kweeseli kwaye bafumanisa ukuba unyango lwe-NMNH lunqande ukukhula kweeseli ze-HepG2 kwiindawo eziphakamileyo ngaphezu kwe-250 μM. Abaphandi bahlalutya umjikelezo weseli kwiiseli ze-HepG2 eziphathwa nge-1 mM NMNH okanye i-NMN kwiiyure ze-12 kwaye zafumanisa ukuba i-NMNH yabangela ukubanjwa kwe-cell cycle, ngelixa i-NMN yayingenayo impembelelo kumjikelezo weseli. Ukongezelela, abaphandi bafumanisa ukuba i-500 μM NMNH ivalwe ngokupheleleyo ukukhula kweeseli ze-786-O; I-250 μM i-NMNH inokuthintela ngokufanelekileyo ukukhula kweeseli kwiiseli ze-HK-2.
Umzobo 7.8.NMNH inqanda ukukhula kweeseli kwi-vitro
04.
NMNHabaphandi bokhuseleko baqhube iimvavanyo zokuba ingaba iidosi eziphezulu ze-NMNH zibangela i-hepatotoxicity. Unyango lweegundane ze-C57BL / 6J zamadoda kunye ne-50, i-100, i-500, okanye i-1000 mg / kg ye-NMNH ngokusebenzisa inaliti ye-intraperitoneal yonke enye imini ngeveki enye ibonise ukuba akukho kuncipha kwi-serum alanine aminotransferase (ALT) kunye namanqanaba e-aspartate aminotransferase (AST). Inyukile, ebonisa ukuba i-NMNH ayinayo i-hepatotoxic kwiidosi eziphezulu. Ukongeza, abaphandi bafumanise ukuba unyango lwe-NMNH lonyuse umxholo we-NAD + kwizibindi zempuku ngendlela exhomekeke kwidosi. Unyango nge-1000 mg / kg i-NMNH yonyuse amanqanaba e-NAD + kwizibindi zegundane ngamaxesha angaphezu kwe-10.
Umfanekiso we-10.
NMNHyonyusa inqanaba le-NAD + kwisibindi seempuku
Izifundo zibonise ukuba i-NMNH iyona engcono ye-NAD + -yokunyusa ukongezelela kune-NMN zombini kwi-vitro nakwi-vivo; ukongeza, i-NMNH inyusa amanqanaba e-NAD (NADH) ancitshisiweyo kwiiseli kunye nezibindi zemouse. Uhlalutyo lwe-Metabolomic lubonise ukuba i-NMNH inqanda i-glycolysis kunye nomjikelezo we-TCA. Uvavanyo lwe-in vitro lubonisa ukuba i-NMNH ibangela ukubanjwa komjikelo weseli kwaye inqanda ukukhula kweeseli. Kuthatyathwe kunye, olu phononongo lubonisa ukuba i-NMNH yi-NAD + enamandla yokuphucula kwaye inqanda i-glycolysis, umjikelo we-TCA, kunye nokukhula kweeseli.
Igama lesiTshayina le-NMNH "liyancipha i-β-nicotinamide mononucleotide", eyona ndlela yokunciphisa i-NMN kunye ne-amorphous yellow powder. Ifomula yemolekyuli: C11H17N2O8P Ubunzima beMolekyuli: 336.23g/molCAS No.: 108347-85-9 Uncwadi lophando lwamva nje lubonisa ukuba i-NMNH yonyusa amanqanaba e-NAD + ngokukhawuleza kwaye kwinqanaba eliphezulu, kwi-avareji ye-5 amaxesha e-NMN
Indlela yempiloNMNHudubulo lokwenyani
