Synergistic activation of mitochondrial metabolism and the glutathione redox couple protects HepG2 hepatocarcinoma cells from palmitoylcarnitine-induced stress
| Autor: | Ali C. Dehghani, Christopher G. R. Perry, Christopher F. Theriau, Patrick C. Turnbull, Michael K. Connor |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Flexibility (anatomy) Physiology Cell Survival Apoptosis Mitochondrion medicine.disease_cause Redox Oxidative Phosphorylation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Humans Uncoupling Protein 2 Buthionine Sulfoximine Palmitoylcarnitine chemistry.chemical_classification Rapid Report Fatty acid Cell Biology Metabolism Glutathione Hep G2 Cells Hydrogen Peroxide HCT116 Cells digestive system diseases Cell biology Mitochondria Oxidative Stress 030104 developmental biology medicine.anatomical_structure chemistry Gene Expression Regulation Organ Specificity 030220 oncology & carcinogenesis HT29 Cells Oxidation-Reduction Oxidative stress |
| Zdroj: | Am J Physiol Cell Physiol |
| ISSN: | 1522-1563 |
| Popis: | Fatty acid stress can have divergent effects in various cancers. We explored how metabolic and redox flexibility in HepG2 hepatocarcinoma cells mediates protection from palmitoylcarnitine. HepG2 cells, along with HCT 116 and HT29 colorectal cancer cells were incubated with 100 μM palmitoylcarnitine for up to 48 h. Mitochondrial H2O2 emission, glutathione, and cell survival were assessed in HT29 and HepG2 cells. 100 μM palmitoylcarnitine promoted early growth in HepG2 cells by ~8% after 48 h versus decreased cell survival observed in HT29 and HCT 116 cells. Palmitoylcarnitine increased mitochondrial respiration at physiological and maximal concentrations of ADP, while lowering cellular lactate content in HepG2 cells, suggesting a switch to mitochondrial metabolism. HepG2 cell growth was associated with an early increase in H2O2 emission by 10 min, followed by a decrease in H2O2 at 24 h that corresponded with increased glutathione content, suggesting a redox-based compensatory mechanism. In contrast, abrogation of HT29 cell proliferation was related to decreased mitochondrial respiration (likely due to cell death) and decreased glutathione. Concurrent glutathione depletion with BSO prevented palmitoylcarnitine-induced growth in HepG2 cells, indicating that glutathione was critical for promoting growth following palmitoylcarnitine. Inhibiting UCP2 with genipin sensitized HepG2 cells to palmitoylcarnitine, suggesting that activation of UCP2 may be a 2nd redox-based mechanism conferring protection. These findings suggest that HepG2 cells possess inherent metabolic and redox flexibility relative to HT29 cells that confers protection from palmitoylcarnitine-induced stress via adaptive increases in mitochondrial respiratory control, glutathione buffering, and induction of UCP2. |
| Databáze: | OpenAIRE |
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