Nicotinamide ameliorates palmitate-induced ER stress in hepatocytes via cAMP/PKA/CREB pathway-dependent Sirt1 upregulation

Biochimica Et Biophysica Acta
Jiaxin LiZhenyuan Song

Abstract

Nicotinamide (NAM) is the amide of nicotinic acid and a predominant precursor for NAD(+) biosynthesis via the salvage pathway. Sirt1 is a NAD(+)-dependent deacetylase, playing an important role in regulating cellular functions. Although hepatoprotective effect of NAM has been reported, the underlying mechanism remains elusive. ER stress, induced by saturated fatty acids, in specific palmitate, plays a pathological role in the development of nonalcoholic fatty liver disease. This study aims to determine the effect of NAM on palmitate-induced ER stress in hepatocytes and to elucidate molecular mechanisms behind. Both HepG2 cells and primary mouse hepatocytes were exposed to palmitate (conjugated to BSA at a 2:1 M ratio), NAM, or their combination for different durations. Cellular NAD(+) level, Sirt1 expression/activity, ER stress, as well as cAMP/PKA/CREB pathway activation were determined. NAM increased Sirt1 expression and enzymatic activity, which contributes to the ameliorative effect of NAM on palmitate-triggered ER stress. NAM increased intracellular NAD(+) level in hepatocytes, however, blocking the salvage pathway, a pathway for NAD(+) synthesis from NAM, only partially prevented NAM-induced Sirt1 upregulation while compl...Continue Reading

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Citations

Apr 20, 2018·Journal of Cellular and Molecular Medicine·Chen ShenZhenyuan Song
Oct 18, 2018·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Li LiuJena J Steinle
Jan 17, 2019·Molecular Neurobiology·Siqi ZhaoShuang Rong
Dec 22, 2017·Journal of the Endocrine Society·Yasir S ElhassanGareth G Lavery
Apr 27, 2019·Experimental & Molecular Medicine·Seung Jin LeeChi Dae Kim
May 17, 2019·Journal of Physiology and Biochemistry·Hajar Shokri AfraMitra Nourbakhsh
Nov 30, 2018·Molecular Medicine Reports·Hai-Feng WanYong Zeng
Mar 25, 2019·Daru : Journal of Faculty of Pharmacy, Tehran University of Medical Sciences·Fahad A Al-AbbasiFiroz Anwar
Apr 19, 2017·Cellular and Molecular Life Sciences : CMLS·Eun Seong Hwang, Seon Beom Song
Feb 2, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rasmi R MishraÖzgür Şahin
Aug 31, 2021·RSC Medicinal Chemistry·Iredia D Iyamu, Rong Huang

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