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

Copper chaperones are copper-binding proteins that directly insert copper into specific targets, preventing the accumulation of free copper ions that can be toxic to the cell. Despite considerable advances in the understanding of copper transfer from copper chaperones to their target, to date, there is no information regarding how the activity of these proteins is regulated in higher eukaryotes. The insertion of copper into the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) depends on the copper chaperone for SOD1 (CCS). We have recently reported that CCS protein is increased in tissues of rats fed copper-deficient diets suggesting that copper may regulate CCS expression. Here we show that whereas copper deficiency increased CCS protein in rats, mRNA level was unaffected. Rodent and human cell lines cultured in the presence of the specific copper chelator 2,3,2-tetraamine displayed a dose-dependent increase in CCS protein that could be reversed with the addition of copper but not iron or zinc to the cells. Switching cells from copper-deficient to copper-rich medium promoted the rapid degradation of CCS, which could be blocked by the proteosome inhibitors MG132 and lactacystin but not a cysteine protease inhibitor or inhibitors of the lysosomal degradation pathway. In addition, CCS degradation was slower in copper-deficient cells than in cells cultured in copper-rich medium. Together, these data show that copper regulates CCS expression by modulating its degradation by the 26 S proteosome and suggest a novel role for CCS in prioritizing the utilization of copper when it is scarce.
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PMID:Copper modulates the degradation of copper chaperone for Cu,Zn superoxide dismutase by the 26 S proteosome. 1283 19

Ischemic stroke is a leading cause of long lasting disability in humans and oxidative stress an important underlying cause. The present study aims to determine the effect of short term (seven-days) administration of high dosage grape seed and skin extract (GSSE 2.5 g/kg) on ischemia/reperfusion (I/R) injury in a rat model of global ischemia. Ischemia was induced by occlusion of the common carotid arteries for 30 min followed by one-hour reperfusion on control or GSSE treated animals. I/R induced a drastic oxidative stress characterized by high lipid and protein oxidation, a drop in antioxidant enzyme defenses, disturbed transition metals as free iron overload and depletion of copper, zinc and manganese as well as of associated brain enzyme activities as glutamine synthetase and lactate dehydrogenase. I/R also induced NO and calcium disruption and an increase in calpain activity, a calcium-sensitive cysteine protease. Interestingly, almost all I/R-induced disturbances were prevented by GSSE pretreatment as oxidative stress, transition metals associated enzyme activities, brain damage size and histology. Owing to its antioxidant potential, high dosage GSSE protected efficiently the brain against ischemic stroke and should be translated to humans.
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PMID:Protective effect of grape seed and skin extract on cerebral ischemia in rat: implication of transition metals. 2536 17

Reproductive sinks regulate monocarpic senescence in wheat as desinking delayed flag leaf senescence under irrigated condition. In this study, wheat cv. HW 2041 and its isonuclear male sterile line (CMS) were subjected to post-anthesis water deficit stress to understand the association between sink strength, senescence and drought response in relation to oxidative stress and antioxidant defense at cellular and sub-cellular level. CMS plants maintained better water relations and exhibited delayed onset and progression of flag leaf senescence in terms of green leaf area, chlorophyll and protein content than fertile plants under water deficit stress (WDS). Delayed senescence in CMS plants under water deficit stress was associated with less reactive oxygen species generation, lower damage to membranes and better antioxidant defense both in terms of antioxidant enzyme activities and metabolite content compared to fertile plants. Expression of some senescence associated genes (SAGs) such as WRKY transcription factor (WRKY53), glutamine synthetase1 (GS1), wheat cysteine protease (WCP2) and wheat serine protease (WSP) was lower while catalse 2 (CAT2) transcript levels were higher in the CMS plants compared to HW2041 during senescence under water deficit stress. Antioxidant defense in chloroplasts was better in CMS line under water deficit stress compared to HW2041. This is the first report showing that reproductive sink enhanced drought induced senescence in flag leaf of wheat fertile line is associated with higher oxidative stress and damage and loss of antioxidant competence compared to its sterile line under water deficit stress. Higher expression of some SAGs and decline in superoxide dismutase and ascorbate peroxidase activity in the chloroplasts also contributed to the accelerated senescence in fertile line compared to its CMS line under WDS.
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PMID:Reproductive sink enhanced drought induced senescence in wheat fertile line is associated with loss of antioxidant competence compared to its CMS line. 3004 15