Low concentration of morphine protects against cell death, oxidative stress and calcium accumulation by nicotine in PC12 cells

1-O-Hexyl-2,3,5-trimethylhydroquinone (HTHQ) has previously been found to have effective anti-oxidant and anti-lipid-peroxidative activity. We aimed to elucidate whether HTHQ can prevent dopaminergic neuronal cell death by investigating the effect on l-DOPA-induced cytotoxicity in PC12 cells. HTHQ protected from both l-DOPA-induced cell death and superoxide dismutase activity reduction. When assessing the effect of HTHQ on oxidative stress-related signaling pathways, HTHQ inhibited l-DOPA-induced phosphorylation of sustained extracellular signal-regulated kinases (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK1/2). HTHQ also normalized l-DOPA-reduced Bcl-2-associated death protein (Bad) phosphorylation and Bcl-2-associated X protein (Bax) expression, promoting cell survival. Taken together, HTHQ exhibits protective effects against l-DOPA-induced cell death through modulation of the ERK1/2-p38MAPK-JNK1/2-Bad-Bax signaling pathway in PC12 cells. These results suggest that HTHQ may show ameliorative effects against oxidative stress-induced dopaminergic neuronal cell death, although further studies in animal models of Parkinson’s disease are required to confirm this.

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Effect of alpha-ketoglutarate and N-acetyl cysteine on cyanide-induced oxidative stress mediated cell death in PC12 cells

Toxicology and Industrial Health ◽

10.1177/0748233710365695 ◽

2010 ◽

Vol 26 (5) ◽

pp. 297-308 ◽

Cited By ~ 13

Author(s):

RM Satpute ◽

J. Hariharakrishnan ◽

R. Bhattacharya

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Pc12 Cells ◽

Caspase 3 ◽

Critical Role ◽

Total Antioxidant Status ◽

Protective Effects ◽

Simultaneous Treatment ◽

Acetyl Cysteine

Cyanide is a mitochondrial poison, which is ubiquitously present in the environment. Cyanide-induced oxidative stress is known to play a key role in mediating the neurotoxicity and cell death in rat pheochromocytoma (PC12) cells. PC12 cells are widely used as a model for neurotoxicity assays in vitro. In the present study, we investigated the protective effects of alpha-ketoglutarate (A-KG), a potential cyanide antidote, and N-acetyl cysteine (NAC), an antioxidant against toxicity of cyanide in PC12 cells. Cells were treated with various concentrations (0.625—1.25 mM) of potassium cyanide (KCN) for 4 hours, in the presence or absence of simultaneous treatment of A-KG (0.5 mM) and NAC (0.25 mM). Cyanide caused marked decrease in the levels of cellular antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). Lipid peroxidation indicated by elevated levels of malondialdehyde (MDA) was found to be accompanied by decreased levels of reduced glutathione (GSH) and total antioxidant status (TAS) of the cells. Cyanide-treated cells showed notable increase in caspase-3 activity and induction of apoptotic type of cell death after 24 hours. A-KG and NAC alone were very effective in restoring the levels of GSH and TAS, but together they significantly resolved the effects of cyanide on antioxidant enzymes, MDA levels, and caspase-3 activity. The present study reveals that combination of A-KG and NAC has critical role in abbrogating the oxidative stress-mediated toxicity of cyanide in PC12 cells. The results suggest potential role of A-KG and NAC in cyanide antagonism.

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Song Bu Li Decoction, a Traditional Uyghur Medicine, Protects Cell Death by Regulation of Oxidative Stress and Differentiation in Cultured PC12 Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/687958 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Maitinuer Maiwulanjiang ◽

Kevin Y. Zhu ◽

Jianping Chen ◽

Abudureyimu Miernisha ◽

Sherry L. Xu ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Pc12 Cells ◽

Stress Proteins ◽

Antioxidant Response ◽

Scientific Basis ◽

Herbal Extract ◽

Dependent Manner ◽

Protein Marker ◽

Dose Dependent

Song Bu Li decoction (SBL) is a traditional Uyghur medicinal herbal preparation, containing Nardostachyos Radix et Rhizoma. Recently, SBL is being used to treat neurological disorders (insomnia and neurasthenia) and heart disorders (arrhythmia and palpitation). Although this herbal extract has been used for many years, there is no scientific basis about its effectiveness. Here, we aimed to evaluate the protective and differentiating activities of SBL in cultured PC12 cells. The pretreatment of SBL protected the cell against tBHP-induced cell death in a dose-dependent manner. In parallel, SBL suppressed intracellular reactive oxygen species (ROS) formation. The transcriptional activity of antioxidant response element (ARE), as well as the key antioxidative stress proteins, was induced in dose-dependent manner by SBL in the cultures. In cultured PC12 cells, the expression of neurofilament, a protein marker for neuronal differentiation, was markedly induced by applied herbal extract. Moreover, the nerve growth factor- (NGF-) induced neurite outgrowth in cultured PC12 cells was significantly potentiated by the cotreatment of SBL. In accord, the expression of neurofilament was increased in the treatment of SBL. These results therefore suggested a possible role of SBL by its effect on neuron differentiation and protection against oxidative stress.

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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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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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Allantopyrone A activates Keap1–Nrf2 pathway and protects PC12 cells from oxidative stress-induced cell death

The Journal of Antibiotics ◽

10.1038/ja.2016.99 ◽

2016 ◽

Vol 70 (4) ◽

pp. 429-434 ◽

Cited By ~ 9

Author(s):

Shota Uesugi ◽

Makoto Muroi ◽

Yasumitsu Kondoh ◽

Yoshihito Shiono ◽

Hiroyuki Osada ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Pc12 Cells ◽

Nrf2 Pathway

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Neuroprotective eects of Breviscapine against oxidative-stress-induced cell death in PC12 cells: Involvement of Nrf2/HO-1 pathway

Medicine Sciences and Bioengineering ◽

10.1201/b18418-56 ◽

2015 ◽

pp. 295-300

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Pc12 Cells

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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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