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

Background. Multiple studies have indicated crucial roles of NAD+ deficiency in several neurological diseases and aging. It is critical to discover the mechanisms underlying the NAD+ deficiency. A decreased level of Nicotinamide phosphoribosyltransferase (Nampt)—an important enzyme in the salvage pathway of NAD+ synthesis—has been found under certain pathological conditions, while the mechanisms underlying the Nampt decrease are unclear. The purpose of this study is to test the hypothesis that oxidative stress can produce decreased Nampt, and to investigate the biological effects of Nampt on NAD+ synthesis and cell survival under both basal and oxidative stress conditions. Methods. We used differentiated PC12 cells as a cellular model to investigate the effects of oxidative stress on the levels of Nampt. Multiple assays, including flow cytometry-based cell death assays and NAD+ assays were conducted. Results. First, oxidative stress can decrease the levels of Nampt mRNA and Nampt protein; second, Nampt plays significant roles in NAD+ synthesis under both basal conditions and oxidative stress conditions; third, Nampt plays critical roles in cell survival under both basal conditions and oxidative stress conditions; and fourth, oxidative stress produced decreased NAD+ levels and cell survival partially by decreasing Nampt. Collectively, our study has indicated that oxidative stress is a pathological factor leading to decreased Nampt, which plays important roles in oxidative stress-produced decreases in NAD+ levels and cell survival. Our findings have indicated major roles of Nampt in maintaining NAD+ levels and cell survival under both basal and oxidative stress conditions.

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NAD+ treatment can increase directly the antioxidant capacity of rotenone-treated differentiated PC12 cells

10.1101/498162 ◽

2018 ◽

Author(s):

Jie Zhang ◽

Yunyi Hong ◽

Wei Cao ◽

Haibo Shi ◽

Weihai Ying

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Antioxidant Capacity ◽

Pc12 Cells ◽

Mitochondrial Permeability Transition ◽

Permeability Transition ◽

Protective Effects ◽

Beneficial Effects ◽

Differentiated Pc12 Cells ◽

Major Index

NAD+ administration can produce profound beneficial effects in the animal models of aging and a number of diseases. Since oxidative stress plays key pathological roles in aging and multiple major disorders, it is crucial to elucidate the mechanisms underlying the protective effects of NAD+ administration on oxidative stress-induced cell death. Previous studies have suggested that NAD+ treatment can decrease oxidative cell death indirectly by such mechanisms as preventing mitochondrial permeability transition, while it is unclear if NAD+ administration may decrease oxidative cell death by increasing directly the antioxidant capacity of the cells. Our current study used rotenone-treated differentiated PC12 cells as a cellular model to test our hypothesis that NAD+ treatment may increase directly the antioxidant capacity of the cells exposed to oxidative stress. Our study has indicated that NAD+ treatment can significantly attenuate the rotenone-induced increase in oxidative stress in the cells. Moreover, NAD+ treatment can significantly enhance the GSH/GSSG ratio, a major index of antioxidant capacity, of rotenone-treated cells. Collectively, our study has provided the first evidence indicating that NAD+ treatment can increase directly the antioxidant capacity of cells exposed to oxidative stress. These findings have suggested a novel mechanism underlying the profound protective effects of NAD+ administration in numerous disease models: NAD+ administration can decrease oxidative stress-induced cell death by enhancing directly the antioxidant capacity of the cells. Our finding has also highlighted the nutritional potential of NAD+.

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Protective Effects of Selol Against Sodium Nitroprusside-Induced Cell Death and Oxidative Stress in PC12 Cells

Neurochemical Research ◽

10.1007/s11064-016-2046-2 ◽

2016 ◽

Vol 41 (12) ◽

pp. 3215-3226 ◽

Cited By ~ 5

Author(s):

Agnieszka Dominiak ◽

Anna Wilkaniec ◽

Piotr Wroczyński ◽

Henryk Jęśko ◽

Agata Adamczyk

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Sodium Nitroprusside ◽

Pc12 Cells ◽

Protective Effects ◽

And Oxidative Stress

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

10.1101/2020.08.20.259143 ◽

2020 ◽

Author(s):

Cuiyan Zhou ◽

Weihai Ying

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Pc12 Cells ◽

Mrna Levels ◽

Salvage Pathway ◽

Nicotinamide Phosphoribosyltransferase ◽

Protein Levels ◽

Pathological Conditions ◽

Important Enzyme

AbstractNumerous 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.

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