DOI: 10.1101/497404Dec 15, 2018Paper

SIRT2, ERK and Nrf2 mediate NAD+ treatment-induced increase in the antioxidant capacity of differentiated PC12 cells under basal conditions

BioRxiv : the Preprint Server for Biology
Jie ZhangWeihai Ying

Abstract

NAD+ administration is highly beneficial in numerous models of diseases and aging. It is becoming increasingly important to determine if NAD+ treatment may increase directly the antioxidant capacity of cells under basal conditions. In current study we tested our hypothesis that NAD+ can enhance directly antioxidant capacity of cells under basal conditions by using differentiated PC12 cells as a cellular model. We found that NAD+ treatment can increase the GSH/GSSG ratios in the cells under basal conditions. NAD+ can also increase both the mRNA and protein level of gamma-glutamylcysteine ligase, a key enzyme for glutathione synthesis, which appears to be mediated by the NAD+-induced increase in Nrf2 activity. These NAD+-induced changes can be prevented by both SIRT2 siRNA and the SIRT2 inhibitor AGK2. The NAD+-induced changes can also be blocked by the ERK signaling inhibitor U0126. Moreover, the NAD+-induced ERK activation can be blocked by both SIRT2 siRNA and AGK2. Collectively, our study has provided the first evidence that NAD+ can enhance directly the antioxidant capacity of the cells under basal conditions, which is mediated by SIRT2, ERK, and Nrf2. These findings have suggested not only the great nutritional potential of...Continue Reading

Related Concepts

Aging
Antioxidants
Glutathione
Nicotinamide adenine dinucleotide (NAD)
Oxidation
RNA, Messenger
Gamma-glutamylcysteine
PC12 Cells
Dysplastic Nevus
Inhibitors

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