scholarly journals High Glucose-Induced PC12 Cell Death by Increasing Glutamate Production and Decreasing Methyl Group Metabolism

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Minjiang Chen ◽  
Hong Zheng ◽  
Tingting Wei ◽  
Dan Wang ◽  
Huanhuan Xia ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cell Death ◽  
Pc12 Cells ◽  
High Glucose ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Creatine Phosphate ◽  
Metabolic Changes ◽  
Extracellular Medium ◽  
Methyl Group

Objective. High glucose- (HG-) induced neuronal cell death is responsible for the development of diabetic neuropathy. However, the effect of HG on metabolism in neuronal cells is still unclear.Materials and Methods. The neural-crest derived PC12 cells were cultured for 72 h in the HG (75 mM) or control (25 mM) groups. We used NMR-based metabolomics to examine both intracellular and extracellular metabolic changes in HG-treated PC12 cells.Results. We found that the reduction in intracellular lactate may be due to excreting more lactate into the extracellular medium under HG condition. HG also induced the changes of other energy-related metabolites, such as an increased succinate and creatine phosphate. Our results also reveal that the synthesis of glutamate from the branched-chain amino acids (isoleucine and valine) may be enhanced under HG. Increased levels of intracellular alanine, phenylalanine, myoinositol, and choline were observed in HG-treated PC12 cells. In addition, HG-induced decreases in intracellular dimethylamine, dimethylglycine, and 3-methylhistidine may indicate a downregulation of methyl group metabolism.Conclusions. Our metabolomic results suggest that HG-induced neuronal cell death may be attributed to a series of metabolic changes, involving energy metabolism, amino acids metabolism, osmoregulation and membrane metabolism, and methyl group metabolism.

scholarly journals Aurintricarboxylic acid rescues PC12 cells and sympathetic neurons from cell death caused by nerve growth factor deprivation: correlation with suppression of endonuclease activity.

1991 ◽  
Vol 115 (2) ◽  
pp. 461-471 ◽  
Author(s):  
A Batistatou ◽  
L A Greene
Keyword(s):  
Cell Death ◽  
Nerve Growth Factor ◽  
Pc12 Cells ◽  
Sympathetic Neurons ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Endonuclease Activity ◽  
Term Survival ◽  
Serum Free

Past studies have shown that serum-free cultures of PC12 cells are a useful model system for studying the neuronal cell death which occurs after neurotrophic factor deprivation. In this experimental paradigm, nerve growth factor (NGF) rescues the cells from death. It is reported here that serum-deprived PC12 cells manifest an endonuclease activity that leads to internucleosomal cleavage of their cellular DNA. This activity is detected within 3 h of serum withdrawal and several hours before any morphological sign of cell degeneration or death. NGF and serum, which promote survival of the cells, inhibit the DNA fragmentation. Aurintricarboxylic acid (ATA), a general inhibitor of nucleases in vitro, suppresses the endonuclease activity and promotes long-term survival of PC12 cells in serum-free cultures. This effect appears to be independent of macromolecular synthesis. In addition, ATA promotes long-term survival of cultured sympathetic neurons after NGF withdrawal. ATA neither promotes nor maintains neurite outgrowth. It is hypothesized that the activation of an endogenous endonuclease could be responsible for neuronal cell death after neurotrophic factor deprivation and that growth factors could promote survival by leading to inhibition of constitutively present endonucleases.

scholarly journals 1-O-Hexyl-2,3,5-Trimethylhydroquinone Ameliorates l-DOPA-Induced Cytotoxicity in PC12 Cells

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 867 ◽  
Author(s):  
Hyun Park ◽  
Jong Kang ◽  
Myung Lee
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Pc12 Cells ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Extracellular Signal ◽  
Dopaminergic Neuronal Cell ◽  
Mitogen Activated Protein

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.

scholarly journals Hericium Erinaceus Prevents DEHP-Induced Mitochondrial Dysfunction and Apoptosis in PC12 Cells

2020 ◽  
Vol 21 (6) ◽  
pp. 2138 ◽  
Author(s):  
Ines Amara ◽  
Maria Scuto ◽  
Agata Zappalà ◽  
Maria Laura Ontario ◽  
Antonio Petralia ◽  
...  
Keyword(s):  
Cell Death ◽  
Protective Effect ◽  
Pc12 Cells ◽  
Antioxidant Activities ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Hericium Erinaceus ◽  
Nutritional Strategy ◽  
Induced Apoptosis ◽  
Ethylhexyl Phthalate

Hericium Erinaceus (HE) is a medicinal plant known to possess anticarcinogenic, antibiotic, and antioxidant activities. It has been shown to have a protective effect against ischemia-injury-induced neuronal cell death in rats. As an extending study, here we examined in pheochromocytoma 12 (PC12) cells, whether HE could exert a protective effect against oxidative stress and apoptosis induced by di(2-ethylhexyl)phthalate (DEHP), a plasticizer known to cause neurotoxicity. We demonstrated that pretreatment with HE significantly attenuated DEHP induced cell death. This protective effect may be attributed to its ability to reduce intracellular reactive oxygen species levels, preserving the activity of respiratory complexes and stabilizing the mitochondrial membrane potential. Additionally, HE pretreatment significantly modulated Nrf2 and Nrf2-dependent vitagenes expression, preventing the increase of pro-apoptotic and the decrease of anti-apoptotic markers. Collectively, our data provide evidence of new preventive nutritional strategy using HE against DEHP-induced apoptosis in PC12 cells.

scholarly journals Effect of 8-hydroxyquinoline and derivatives on human neuroblastoma SH-SY5Y cells under high glucose

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2389 ◽  
Author(s):  
Wilasinee Suwanjang ◽  
Supaluk Prachayasittikul ◽  
Virapong Prachayasittikul
Keyword(s):  
Cell Death ◽  
Intracellular Calcium ◽  
Signaling Pathways ◽  
High Glucose ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Human Neuroblastoma ◽  
Beneficial Effects ◽  
Therapeutic Development ◽  
Multifunctional Properties

8-Hydroxyquinoline and derivatives exhibit multifunctional properties, including antioxidant, antineurodegenerative, anticancer, anti-inflammatory and antidiabetic activities. In biological systems, elevation of intracellular calcium can cause calpain activation, leading to cell death. Here, the effect of 8-hydroxyquinoline and derivatives (5-chloro-7-iodo-8-hydroxyquinoline or clioquinol and 8-hydroxy-5-nitroquinoline or nitroxoline) on calpain-dependent (calpain-calpastatin) pathways in human neuroblastoma (SH-SY5Y) cells was investigated. 8-Hydroxyquinoline and derivatives ameliorated high glucose toxicity in SH-SY5Y cells. The investigated compounds, particularly clioquinol, attenuated the increased expression of calpain, even under high-glucose conditions. 8-Hydroxyquinoline and derivatives thus adversely affected the promotion of neuronal cell death by high glucose via the calpain-calpastatin signaling pathways. These findings support the beneficial effects of 8-hydroxyquinolines for further therapeutic development.

scholarly journals Suppression of Extensive Neurofilament Phosphorylation Rescues α-Internexin/Peripherin-Overexpressing PC12 Cells from Neuronal Cell Death

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e43883 ◽  
Author(s):  
Wen-Ching Lee ◽  
Daphne Kan ◽  
Yun-Yu Chen ◽  
Shan-Kuo Han ◽  
Kuo-Shyan Lu ◽  
...  
Keyword(s):  
Cell Death ◽  
Pc12 Cells ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Neurofilament Phosphorylation
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