ArticleCancer research2012
Manganese superoxide dismutase regulates a metabolic switch during the mammalian cell cycle.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 66 citations in OpenAlex.
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- MnSOD Lysine 68 acetylation leads to cisplatin and doxorubicin resistance due to aberrant mitochondrial metabolism.International journal of biological sciences · 2021Article
- Arachidonate 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid contribute to stromal aging-induced progression of pancreatic cancer.The Journal of biological chemistry · 2020Article
- Mitochondrial Superoxide Dismutase: What the Established, the Intriguing, and the Novel Reveal About a Key Cellular Redox Switch.Antioxidants & redox signaling · 2020Review
- Cubic Membranes Formation in Synchronized Human Hepatocellular Carcinoma Cells Reveals a Possible Role as a Structural Antioxidant Defense System in Cell Cycle Progression.Frontiers in cell and developmental biology · 2020Article
- Toll-like receptor 2 regulates metabolic reprogramming in gastric cancer via superoxide dismutase 2.International journal of cancer · 2019Article
- Redox Mechanisms in Neurodegeneration: From Disease Outcomes to Therapeutic Opportunities.Antioxidants & redox signaling · 2019Review
- Pharmacological Ascorbate as a Means of Sensitizing Cancer Cells to Radio-Chemotherapy While Protecting Normal Tissue.Seminars in radiation oncology · 2019Review
- Redox Paradox: A Novel Approach to Therapeutics-Resistant Cancer.Antioxidants & redox signaling · 2018Review
- Prion protein cleavage fragments regulate adult neural stem cell quiescence through redox modulation of mitochondrial fission and SOD2 expression.Cellular and molecular life sciences : CMLS · 2018Article
- Article
- Superoxide Dismutases in Pancreatic Cancer.Antioxidants (Basel, Switzerland) · 2017Review
- Substrate-analog binding and electrostatic surfaces of human manganese superoxide dismutase.Journal of structural biology · 2017Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Proliferating cells consume more glucose to cope with the bioenergetics and biosynthetic demands of rapidly dividing cells as well as to counter a shift in cellular redox environment. This study investigates the hypothesis that manganese superoxide dismutase (MnSOD) regulates cellular redox flux and glucose consumption during the cell cycle. A direct correlation was observed between glucose consumption and percentage of S-phase cells in MnSOD wild-type fibroblasts, which was absent in MnSOD homozygous knockout fibroblasts. Results from electron paramagnetic resonance spectroscopy and flow cytometric assays showed a significant increase in cellular superoxide levels in S-phase cells, which was associated with an increase in glucose and oxygen consumption, and a decrease in MnSOD activity. Mass spectrometry results showed a complex pattern of MnSOD-methylation at both lysine (68, 89, 122, and 202) and arginine (197 and 216) residues. MnSOD protein carrying a K89A mutation had significantly lower activity compared with wild-type MnSOD. Computational-based simulations indicate that lysine and arginine methylation of MnSOD during quiescence would allow greater accessibility to the enzyme active site as well as increase the positive electrostatic potential around and within the active site. Methylation-dependent changes in the MnSOD conformation and subsequent changes in the electrostatic potential around the active site during quiescence versus proliferation could increase the accessibility of superoxide, a negatively charged substrate. These results support the hypothesis that MnSOD regulates a "metabolic switch" during progression from quiescent through the proliferative cycle. We propose MnSOD as a new molecular player contributing to the Warburg effect.
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Registered trials
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