Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this work was to test the hypothesis that endurance training may be protective against in vivo doxorubicin (DOX)-induced cardiomyopathy through mitochondria-mediated mechanisms. Forty adult (6-8 wk old) male Wistar rats were randomly divided into four groups (n = 10/group): nontrained, nontrained + DOX treatment (20 mg/kg), trained (14 wk of endurance treadmill running, 60-90 min/day), and trained + DOX treatment. Mitochondrial respiration, calcium tolerance, oxidative damage, heat shock proteins (HSPs), antioxidant enzyme activity, and apoptosis markers were evaluated. DOX induces mitochondrial respiratory dysfunction, oxidative damage, and histopathological lesions and triggers apoptosis (P < 0.05, n = 10). However, training limited the decrease in state 3 respiration, respiratory control ratio (RCR), uncoupled respiration, aconitase activity, and protein sulfhydryl content caused by DOX treatment and prevented the increased sensitivity to calcium in nontrained + DOX-treated rats (P < 0.05, n = 10). Moreover, training inhibited the DOX-induced increase in mitochondrial protein carbonyl groups, malondialdehyde, Bax, Bax-to-Bcl-2 ratio, and tissue caspase-3 activity (P < 0.05, n = 10). Training also increased by approximately 2-fold the expression of mitochondrial HSP-60 and tissue HSP-70 (P < 0.05, n = 10) and by approximately 1.5-fold the activity of mitochondrial and cytosolic forms of SOD (P < 0.05, n = 10). We conclude that endurance training protects heart mitochondrial respiratory function from the toxic effects of DOX, probably by improving mitochondrial and cell defense systems and reducing cell oxidative stress. In addition, endurance training limited the DOX-triggered apoptosis.
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PMID:Moderate endurance training prevents doxorubicin-induced in vivo mitochondriopathy and reduces the development of cardiac apoptosis. 1579 86

Even though the deleterious effects of increased reactive oxygen species (ROS) levels have been implicated in a variety of neurodegenerative disorders, the triggering events that lead to the increased ROS and successive damages are still ill-defined. Mitochondria are the key organelles controlling the ROS balance, being their main source and also counteracting them by the action of the ROS scavenging system. Mitochondria, moreover, control the presence of ROS-damaged proteins by action of the protein quality control (PQC) system. One of its components is the mitochondrial chaperone Hsp60 assisting the folding of a subset of mitochondrial matrix proteins. Mutations in Hsp60 cause a late onset form of the neurodegenerative disease hereditary spastic paraplegia (SPG13). In this study, we aimed to address the molecular consequences of Hsp60 shortage. We here demonstrate that a heterozygous knockout Hsp60 model that recapitulates features of the human disease and exhibits increased oxidative stress in neuronal tissues. Moreover, we indicate that the increase of ROS is, at least in part, due to impaired folding of the manganese superoxide dismutase (MnSOD), a key antioxidant enzyme. We observed that the Hsp60 and MnSOD proteins interact. Based on these results, we propose that MnSOD is a substrate of the Hsp60 folding machinery and that under conditions of diminished availability of Hsp60, MnSOD is impaired in reaching the native state. This suggests a possible link between Hsp60-dependent PQC and the ROS scavenging systems that may have the function to increase ROS production under conditions of folding stress.
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PMID:The Hsp60 folding machinery is crucial for manganese superoxide dismutase folding and function. 2415 36