Ataxin-3 (ATXN3), the disease protein in spinocerebellar ataxia type 3 (SCA3), binds to target gene promoters and modulates transcription by interaction with transcriptional regulators. Here, we show that ATXN3 interacts with the forkhead box O (FOXO) transcription factor FOXO4 and activates the FOXO4-dependent transcription of the manganese superoxide dismutase (SOD2) gene. Upon oxidative stre...

The development and progression of hepatocellular carcinoma (HCC) is accompanied with persistent oxidative stress, but the molecular basis is not well defined. Superoxide dismutase 2 (SOD2) is an important mitochondrial antioxidant and a key aging factor. Here we investigated the expression and clinical significance of SOD2 in a large cohort of HBV-positive HCC tumors. Both SOD2 mRNA and protei...

Cellular superoxide radicals (O(2)(-)) are mostly generated during mitochondrial oxygen metabolism. O(2)(-) serves as the raw material for many reactive oxygen species (ROS) members like H(2)O(2) and OH(.-) radicals following its catalysis by superoxide dismutase (SOD) enzymes and also by autocatalysis (autodismutation) reactions. Mitochondrial ROS generation could have serious implications on ...

Manganese superoxide dismutase, encoded by the Sod2 gene, is a ubiquitously expressed mitochondrial antioxidant enzyme that is essential for mammalian life. Mice born with constitutive genetic knockout of Sod2 do not survive the neonatal stage, which renders the longitudinal study of the biochemical and metabolic effects of Sod2 loss difficult. However, multiple studies have demonstrated that t...

Mitochondrial superoxide dismutase (SOD2) prevents accumulation of the superoxide that arises as a consequence of oxidative phosphorylation. However, SOD2 is a target of oxidative/nitrosative inactivation, and reduced SOD2 activity has been demonstrated to contribute to portal hypertensive gastropathy. We investigated the consequences of gastric parietal cell-specific SOD2 deficiency on mitocho...

Reactive oxygen species (ROS) act as a mediator of ionizing radiation-induced cellular damage. Previous studies have indicated that MnSOD (SOD2) plays a critical role in protection against ionizing radiation in mammalian cells. In this study, we constructed two types of stable HeLa cell lines overexpressing SOD2, HeLa S3/SOD2 and T-REx HeLa/SOD2, to elucidate the mechanisms underlying the prote...

PURPOSE Advanced prostate cancer is first treated with androgen deprivation therapy. However, tumors become resistant to and grow despite castrate levels of testosterone. Growth and proliferation of CRPC is mediated by gain-of-function changes in the AR and AR reactivation. Expression of manganese superoxide dismutase (SOD2), which regulates cellular ROS, is markedly down-regulated in CRPC when...

Hyperglycemia-induced oxidative stress is an inciting event in the development of diabetic complications including diabetic neuropathy. Our observations of significant oxidative stress and morphological abnormalities in mitochondria led us to examine manganese superoxide dismutase (SOD2), the enzyme responsible for mitochondrial detoxification of oxygen radicals. We demonstrate that overexpress...

In the fission yeast Schizosaccharomyces pombe, the Na+/H+ exchanger, Sod2, plays a major role in the removal of excess intracellular sodium, and its disruption results in a sodium-sensitive phenotype. We examined the subcellular distribution and dynamics of Sod2 expression in S. pombe using a sod2-GFP fusion protein under the control of an attenuated version of the inducible nmt promoter. Sod2...