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Lub hwj chim nyob hauv qab ntawm lub ntiaj teb tiv thaiv kev laus - NMNH

Xov xwm

Lub hwj chim nyob hauv qab ntawm lub ntiaj teb tiv thaiv kev laus - NMNH

2024-08-27 10:00:38 dr hab


Txij li thaum nrhiav tau ntawm NMN los ntawm pab pawg ntawm Harvard tus xibfwb David Sinclair hauv 2013, NMN tau txuas ntxiv ua neeg nyiam hauv zej zog tiv thaiv kev laus thiab paub thiab siv los ntawm ntau tus neeg. Txawm li cas los xij, hauv 2021, pab pawg ntawm xibfwb Deng Haiteng ntawm Tsinghua University tau luam tawm ib tsab xov xwm hu ua "Raws Nicotinamide Mononucleotide (NMNH) Muaj Peev Xwm Txhim Kho NAD + thiab Txhawb Nqa Glycolysis, TCA Cycle, thiab Cell Growth" hauv "Journal of Proteome Research", qhia. : Raws li hom tshiab NAD + ntxiv,NMNHmuaj peev xwm tiv thaiv kev laus zoo hauv vivo thiab hauv vitro dua NMN.

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01.NMNHnce cellular NAD + thiab NADH qib. Cov kws tshawb fawb piv cov teebmeem ntawm NMN thiab NMNH ntawm kev nce cellular NAD + qib. Kev kho mob nrog NMNH (100 μM) nce cellular NAD + qib los ntawm 5-fold hauv HepG2 hlwb, whereas 100 μM NMN tsuas yog me ntsis nce NAD + ntau ntau. Ntxiv rau HepG2 hlwb, cov kws tshawb fawb kuj tau lees paub tias NMNH txhim kho NAD + hauv ES-2 hlwb thiab 3T3-L1 hlwb, uas yog tib neeg lub zes qe menyuam los ntawm cov hlwb thiab nas embryonic fibroblast-derived hlwb, feem. Thiab cov kws tshawb fawb kuj pom tias NMNH nce cellular NAD + qib hauv 786-O hlwb nyob rau hauv lub sij hawm- thiab concentration-dependent yam. Cov kws tshawb fawb tau ntsuas NADH siv qhov loj spectrometry thiab pom tias NADH qib hauv NMNH-kho HepG2 hlwb yog 2.5 npaug siab dua li cov hlwb tsis kho thiab NMN-kho, thiab nce NADH qib kuj tau kuaj pom hauv NMNH-kho 786-O hlwb. Peb kuj pom tias 340 mg / kg NMNH kev kho mob nce NADH qib hauv nas lub siab los ntawm 3-fold, thaum 340 mg / kg NMN kev kho mob nce NADH qib los ntawm 1.7-fold.
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Daim duab 1.2. NMNH nce NAD + qib

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Daim duab 3.4. NMNH nce qib NMNH

02NMNH inhibits glycolysis thiab TCA voj voog. Kev sib sau ntawm NADH qeeb glycolysis thiab TCA voj voog. Txhawm rau tshuaj xyuas cov lus teb metabolic ntawm cov hlwb rau kev kho NMNH, cov kws tshawb fawb tau ua cov tshuaj ntsuam xyuas metabolic ntawmNMNH-thiab NMN-kho cov hlwb. Nws tau pom tias kev kho NMNH tsis tsuas yog txo cov qib ntawm glycolysis intermediates, tab sis kuj txo cov theem ntawm TCA voj voog intermediates. Cov txiaj ntsig no qhia tau hais tias kev sib sau ntawm NADH tsim los ntawm NMNH inhibits cellular glycolysis thiab TCA voj voog.
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Daim duab 5. Txo glycolysis thiab TCA cycle intermediates

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Daim duab 6. Kev tshuaj ntsuam metabolic

03.NMNHinhibits cell loj hlob Cov kws tshawb fawb tshawb fawb txog cov txiaj ntsig ntawm NMNH ntawm kev loj hlob ntawm tes thiab pom tias kev kho NMNH inhibited HepG2 cell loj hlob ntawm qhov siab tshaj 250 μM. Cov kws tshawb fawb tau tshuaj xyuas lub voj voog ntawm tes hauv HepG2 hlwb kho nrog 1 mM NMNH lossis NMN rau 12 teev thiab pom tias NMNH ua rau lub voj voog ntawm tes raug ntes, thaum NMN tsis muaj kev cuam tshuam rau lub voj voog ntawm tes. Tsis tas li ntawd, cov kws tshawb fawb kuj pom tias 500 μM NMNH tag nrho thaiv kev loj hlob ntawm 786-O hlwb; 250 μM NMNH tuaj yeem cuam tshuam kev loj hlob ntawm tes hauv HK-2 hlwb.
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Daim duab 7.8.NMNH inhibits cell loj hlob hauv vitro

04 ib.NMNHCov kws tshawb fawb txog kev nyab xeeb tau ua cov kev sim seb puas muaj ntau npaum li cas ntawm NMNH induce hepatotoxicity. Kev kho mob ntawm C57BL / 6J txiv neej nas nrog 50, 100, 500, lossis 1000 mg / kg NMNH ntawm kev txhaj tshuaj intraperitoneal txhua hnub rau ib lub lis piam qhia tias tsis muaj qhov txo qis hauv cov ntshav alanine aminotransferase (ALT) thiab aspartate aminotransferase (AST) qib. Nce, qhia tias NMNH tsis yog hepatotoxic ntawm koob tshuaj ntau. Tsis tas li ntawd, cov kws tshawb fawb kuj pom tias kev kho NMNH nce NAD + cov ntsiab lus hauv nas lub siab nyob rau hauv koob tshuaj. Kev kho mob nrog 1000 mg / kg NMNH nce qib NAD + hauv nas lub siab los ntawm ntau dua 10 npaug.
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Daim duab 10.NMNHnce qib ntawm NAD + hauv daim siab ntawm nas

Cov kev tshawb fawb tau pom tias NMNH yog ib qho zoo dua NAD +-boosting ntxiv tshaj NMN ob qho tib si hauv vitro thiab hauv vivo; Tsis tas li ntawd, NMNH nce txo NAD (NADH) qib hauv cov hlwb thiab nas lub siab. Metabolomic tsom xam pom tias NMNH inhibits glycolysis thiab TCA voj voog. Kev sim hauv vitro qhia tias NMNH ua rau lub voj voog ntawm tes raug ntes thiab inhibits cell loj hlob. Ua ke, txoj kev tshawb no qhia tau hais tias NMNH yog lub zog NAD + txhim kho thiab inhibits glycolysis, TCA voj voog, thiab kev loj hlob ntawm tes.

Suav lub npe ntawm NMNH yog "txo β-nicotinamide mononucleotide", uas yog txo daim ntawv ntawm NMN thiab yog amorphous daj hmoov. Cov mis mos Molecular: C11H17N2O8P Molecular hnyav: 336.23g / molCAS No.: 108347-85-9 Cov ntaub ntawv tshawb fawb tshiab qhia tau hais tias NMNH nce NAD + ntau dua sai dua thiab ntau dua, qhov nruab nrab 5 npaug ntawm NMN
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Txoj kev noj qab haus huvNMNHtxhaj tshuaj tiag

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