Premium
Delayed treatment of NAD+ can restore intracellular ATP levels and prevent PC12 cell death induced by oxidative stress
Author(s) -
Chen Heyu,
Zhao Cuiping,
Shao Jiaxiang,
Chen Chen,
Xia Weiliang,
Ying Weihai
Publication year - 2010
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.24.1_supplement.lb471
Subject(s) - nad+ kinase , intracellular , oxidative stress , programmed cell death , oxidative phosphorylation , cell , chemistry , microbiology and biotechnology , biochemistry , apoptosis , biology , enzyme
Our studies have shown that NAD+ treatment can greatly decreased the infarct formation in a rat model of brain ischemia. However, the mechanisms underlying the effects of NAD+ remain unclear. In this study we tested our hypothesis that NAD+ attenuates oxidative stress‐induced cell death by restoring intracellular ATP levels. Our study applying LDH assay shows that H2O2‐induced PC 12 cell death was completely prevented when 5 mM NAD+ was added one hr after H2O2 treatment. We also applied luciferase‐based ATP assay to show that four hrs after H2O2 treatment the intracellular ATP levels in the cells were profoundly decreased, which were increased by nearly three folds by NAD+ (5 mM) post‐treatment at one hr after H2O2 exposures (p<0.001). In contrast, post‐treatment of the cells with 5 mM pyruvate at one hr after H2O2 exposures did not restore the ATP levels. Due to the critical roles of ATP in cell survival, our studies suggest that the NAD+‐produced profound protection against oxidative stress‐induced cell death is at least partially mediated by its capacity of restoring intracellular ATP levels. (Supported by a key basic research grant from Shanghai Municipal Scientific Committee (to W.Y.), and a National 973 Program Grant #2010CB834306 (to W.Y. and W. X)).