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Sedoheptulose-1,7-bisphospate Accumulation and Metabolic Anomalies in Hepatoma Cells Exposed to Oxidative Stress
- Source :
- Oxidative Medicine and Cellular Longevity, Vol 2019 (2019), Oxidative Medicine and Cellular Longevity
- Publication Year :
- 2019
- Publisher :
- Hindawi Limited, 2019.
-
Abstract
- We have previously shown that GSH depletion alters global metabolism of cells. In the present study, we applied a metabolomic approach for studying the early changes in metabolism in hydrogen peroxide- (H2O2-) treated hepatoma cells which were destined to die. Levels of fructose 1,6-bisphosphate and an unusual metabolite, sedoheptulose 1,7-bisphosphate (S-1,7-BP), were elevated in hepatoma Hep G2 cells. Deficiency in G6PD activity significantly reduced S-1,7-BP formation, suggesting that S-1,7-BP is formed in the pentose phosphate pathway as a response to oxidative stress. Additionally, H2O2treatment significantly increased the level of nicotinamide adenine dinucleotide phosphate (NADP+) and reduced the levels of ATP and NAD+. Severe depletion of ATP and NAD+in H2O2-treated Hep G2 cells was associated with cell death. Inhibition of PARP-mediated NAD+depletion partially protected cells from death. Comparison of metabolite profiles of G6PD-deficient cells and their normal counterparts revealed that changes in GSH and GSSG per se do not cause cell death. These findings suggest that the failure of hepatoma cells to maintain energy metabolism in the midst of oxidative stress may cause cell death.
- Subjects :
- 0301 basic medicine
Aging
Carcinoma, Hepatocellular
Article Subject
Metabolite
Pentose phosphate pathway
medicine.disease_cause
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
medicine
Humans
lcsh:QH573-671
lcsh:Cytology
Liver Neoplasms
Hydrogen Peroxide
Cell Biology
General Medicine
Metabolism
Heptoses
Molecular biology
Hep G2
Oxidative Stress
030104 developmental biology
Sedoheptulose
chemistry
030220 oncology & carcinogenesis
NAD+ kinase
Nicotinamide adenine dinucleotide phosphate
Oxidative stress
Research Article
Subjects
Details
- ISSN :
- 19420994 and 19420900
- Volume :
- 2019
- Database :
- OpenAIRE
- Journal :
- Oxidative Medicine and Cellular Longevity
- Accession number :
- edsair.doi.dedup.....2cfa0a33aeaa0157bcdc45fa4abca153