(−)Schisandrin B ameliorates paraquat-induced oxidative stress by suppressing glutathione depletion and enhancing glutathione recovery in differentiated PC12 cells

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

PeerJ ◽

10.7717/peerj.11401 ◽

2021 ◽

Vol 9 ◽

pp. e11401

Author(s):

Cuiyan Zhou ◽

Weihai Ying

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Cell Survival ◽

Pc12 Cells ◽

Neurological Diseases ◽

Biological Effects ◽

Stress Conditions ◽

Nicotinamide Phosphoribosyltransferase ◽

Differentiated Pc12 Cells ◽

And Oxidative Stress

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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Cross-talk between cell cycle induction and mitochondrial dysfunction during oxidative stress and nerve growth factor withdrawal in differentiated PC12 cells

Journal of Neuroscience Research ◽

10.1002/jnr.22665 ◽

2011 ◽

Vol 89 (8) ◽

pp. 1302-1315 ◽

Cited By ~ 10

Author(s):

Maria Rosaria Bianco ◽

Miluscia Berbenni ◽

Flavio Amara ◽

Sandra Viggiani ◽

Martina Fragni ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Cycle ◽

Nerve Growth Factor ◽

Growth Factor ◽

Mitochondrial Dysfunction ◽

Pc12 Cells ◽

Cross Talk ◽

Nerve Growth ◽

Differentiated Pc12 Cells ◽

Nerve Growth Factor Withdrawal

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Triptolide attenuated injury via inhibiting oxidative stress in Amyloid-Beta25–35-treated differentiated PC12 cells

Life Sciences ◽

10.1016/j.lfs.2015.12.018 ◽

2016 ◽

Vol 145 ◽

pp. 19-26 ◽

Cited By ~ 14

Author(s):

Pengjuan Xu ◽

Hui Wang ◽

Zhigui Li ◽

Zhuo Yang

Keyword(s):

Oxidative Stress ◽

Pc12 Cells ◽

Differentiated Pc12 Cells

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FAM3A Protects Against Glutamate-Induced Toxicity by Preserving Calcium Homeostasis in Differentiated PC12 Cells

Cellular Physiology and Biochemistry ◽

10.1159/000485943 ◽

2017 ◽

Vol 44 (5) ◽

pp. 2029-2041 ◽

Cited By ~ 7

Author(s):

Qing Song ◽

Wen-Li Gou ◽

Yu-Liang Zou

Keyword(s):

Oxidative Stress ◽

Pc12 Cells ◽

Western Blotting ◽

Molecular Mechanisms ◽

Metabotropic Glutamate Receptor ◽

Protective Effects ◽

Mitochondrial Oxidative Stress ◽

Acid Receptor ◽

Differentiated Pc12 Cells ◽

Ldh Release

Background/Aims: Stroke is the leading cause of adult disability, and glutamate-induced dysregulation of intracellular Ca2+ homeostasis is a key mechanism. FAM3A is the first member of the family with sequence similarity 3 (FAM3) gene family, and its biological function remains largely unknown. We have recently reported that FAM3A exerts protective effects against oxidative stress and mitochondrial dysfunction in HT22 cells. Methods: Here, we investigated the protective effects of FAM3A using a glutamate-induced neuronal injury model in nerve growth factor (NGF)-differentiated PC12 cells. The protective effects were determined by measuring lactate dehydrogenase (LDH) release, apoptosis and mitochondrial oxidative stress. Ca2+ imaging was performed to detect changes in intracellular Ca2+ concentration in PC12 cells. The related molecular mechanisms were investigated by fluorescence staining, coimmunoprecipitation (Co-IP) and western blotting. Results: Upregulation of FAM3A by lentivirus transfection markedly decreased LDH release, inhibited apoptosis and reduced mitochondrial oxidative stress, which were accompanied by alleviated intracellular Ca2+ levels as measured by calcium imaging. The results of western blotting showed that FAM3A significantly decreased the surface expression of metabotropic glutamate receptor 1/5 (mGluR1/5), with no effect on the expression of N-methyl-d-aspartic acid receptor (NMDAR) or α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunits. FAM3A overexpression also inhibited the intracellular Ca2+ release mediated by mGluR1/5 and inositol 1,4,5-trisphosphate receptor (IP3R), but not the ryanodine receptor (RyR). In addition, FAM3A significantly attenuated the store-operated calcium entry (SOCE) induced by thapsigargin (Tg), but the expression of SOCE-related proteins was not altered. The results of coimmunoprecipitation (Co-IP) showed that FAM3A disrupted the interaction of stromal interaction molecule 1 (STIM1) with Orai1 triggered by glutamate. Conclusion: These results suggest that the upregulation of FAM3A protects against glutamate-induced dysfunction of Ca2+ homeostasis not only by inhibiting mGluR1/5-dependent endoplasmic reticulum (ER) Ca2+ release, but also by attenuating SOCE mediated by the STIM1-Orai1 interaction.

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