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Nicotinamide adenine dinucleotide hydrate (NAD+) regulates glucose deprivation‐induced activation of protein O‐GlcNAcylation, ER stress and autophagy (1154.2)
Author(s) -
Zou Luyun,
Chatham John
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1154.2
Subject(s) - autophagy , nad+ kinase , unfolded protein response , chemistry , sirtuin 1 , nicotinamide adenine dinucleotide , microbiology and biotechnology , sirtuin , cellular stress response , cytosol , acetylation , biochemistry , endoplasmic reticulum , biology , apoptosis , downregulation and upregulation , enzyme , fight or flight response , gene
Mammalian sirtuins are important regulators of metabolism and cell survival including autophagy and ER stress. The post‐translational modification of proteins by O‐linked‐N‐acetylglucosamine (O‐GlcNAc) is also metabolically regulated and regulates cell survival responses. We have previously reported that glucose deprivation (GD), which induces autophagy and ER stress is also a potent stimulus for increasing cellular O‐GlcNAc levels. Therefore, the goal of this study, therefore, was to determine whether NAD+, which activates sirtuins, alters the response of GD on protein O‐GlcNAcylation, ER stress, and autophagy. AC16 cardiomyocytes were subjected to GD for up to 24hrs with and without NAD+ (0.25mM). 24hrs after GD there was a significantly increase in O‐GlcNAc levels as well as CHOP, Bip, P‐PERK/T‐PERK and LC3‐II/LC3‐I, consistent with both increased ER stress and activation of autophagy. Treatment with NAD prevented the GD induced increase in O‐GlcNAc and also significantly attenuated both ER stress and autophagic responses. Interestingly GD resulted in a decrease in protein acetylation, which was prevented by NAD, suggesting that the effects of NAD+ may not be mediated via activation of sirtuins, which catalyze deacetylation. Therefore these data indicate that while NAD+ contributes to the regulation of protein O‐GlcNAcylation, ER stress and autophagy this appears to be sirtuin independent. These results also demonstrate for the first time potential cross‐talk between cytosolic redox state and regulation of O‐GlcNAc cycling. Grant Funding Source : Supported by NIH grants HL101192 and HL110366