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

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, H ₂ O ₂ produced significant decreases in both the mRNA levels and the protein levels of Nampt; and third, H ₂ O ₂ 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 H ₂ O ₂ -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 H ₂ O ₂ -induced cell death, suggesting a new mechanism underlying oxidative cell death.