Oxidative stress induces cell death partially by decreasing both mRNA and protein levels of nicotinamide phosphoribosyltransferase in PC12 cells

Abstract

Numerous studies have indicated critical roles of NAD+ deficiency in both aging and multiple major diseases. It is critical to investigate the mechanisms underlying the NAD+ deficiency under the pathological conditions. It has been reported that there was a decreased level of Nicotinamide phosphoribosyltransferase (Nampt) - an important enzyme in the salvage pathway of NAD+ synthesis - under certain pathological conditions, while the mechanisms underlying the Nampt decrease require investigation. In this study we used differentiated PC12 cells as a cellular model to investigate the effects of oxidative stress on both the mRNA and protein levels of Nampt, as well as the role of this effect in oxidative stress-induced cell death: First, Nampt plays significant roles in both the NAD+ synthesis and survival of the cells under basal conditions; second, H2O2 produced significant decreases in both the mRNA levels and the protein levels of Nampt; and third, H2O2 induced cell death partially by producing the decreases in the mRNA and protein levels of Nampt, since the Nampt inhibitor or the Nampt activator significantly exacerbated or attenuated the H2O2-induced cell death, respectively. Collectively, our study has indicated that oxidative stress can decrease both the mRNA and protein levels of Nampt, which has indicated a novel mechanism underlying the NAD+ deficiency in aging and under multiple pathological conditions. Our study has also indicated that the decreased Nampt levels contribute to the H2O2-induced cell death, suggesting a new mechanism underlying oxidative cell death.