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)

Reactive oxygen species are generated physiologically in cells with a significant increase in certain pathological conditions, such as inflammation, cancer, aging, degenerative disease. If endogenous antioxidant systems, in our study represented by glutathione peroxidase, are exceeded by this oxidant flux, tissue injury may occur. Activity of glutathione peroxidase (GPx) was determined using Beutler's modified spectrophotometric assay in erythrocytes from autosomal dominant polycystic kidney disease patients. Activity of glutathione peroxidase was significantly (at p < 0.0001) lower there (17.75 +/- 3.69 U/g haemoglobin) compared to the control group (23.26 +/- .61 U/g Hb). Lower antioxidant enzyme defence system of ADPKD patients, here represented by GPx, can potentiate injury caused by free radicals and possibly play a role in the progression of autosomal dominant polycystic kidney disease.
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PMID:Activity of the antioxidant enzyme, glutathione peroxidase, on autosomal dominant polycystic kidney disease patients. 762 19

Oxidative stress has been implicated in the pathogenesis of both acquired and hereditary polycystic kidney disease. Mechanisms of oxidant injury in C57BL/6J-cpk mice and Han:SPRD-Cy rats with rapidly or slowly progressive polycystic kidney disease were explored. Expression of heme oxygenase-1 mRNA, an inducible marker of oxidative stress, was shown to be increased in cystic kidneys of mice and rats in a pattern that reflected disease severity. By contrast, there was a decrease in mRNA expression of the antioxidant enzymes extracellular glutathione peroxidase, superoxide dismutase, catalase, and glutathione S-transferase during disease progression. Renal mRNA levels of these enzymes were strikingly reduced in rapidly progressive disease in homozygous cystic mice and rats. In slowly progressive disease in heterozygous rats, renal antioxidant mRNA levels were decreased to a greater extent in cystic males than in the less severely affected females. Protein levels for extracellular glutathione peroxidase were also reduced in plasma and in cystic kidneys of mice and rats. Plasma extracellular glutathione peroxidase enzymatic activity was also decreased, whereas the lipid peroxidation products malondialdehyde and 4-hydroxy-2(E)-nonenal were increased in kidneys and blood plasma of cystic mice. Reduced antioxidant enzyme protection and increased oxidative damage represent general mechanisms in the pathogenesis of polycystic kidney disease.
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PMID:Oxidant stress and reduced antioxidant enzyme protection in polycystic kidney disease. 1191 58

Tolvaptan, a vasopressin type 2 receptor antagonist initially developed to increase free-water diuresis, has been approved for the treatment of autosomal dominant polycystic kidney disease in multiple countries. Furthermore, tolvaptan has been shown to improve the renal functions in rodent models of chronic kidney disease (CKD); however, the underlying molecular mechanisms remain unknown. CKD is characterized by increased levels of oxidative stress, and an antioxidant transcription factor-nuclear factor erythroid 2-related factor 2 (Nrf2)-has been gaining attention as a therapeutic target. Therefore, we investigated the effects of tolvaptan and a well-known Nrf2 activator, bardoxolone methyl (BARD) on Nrf2. To determine the role of tolvaptan, we used a renal cortical collecting duct (mpkCCD) cell line and mouse kidneys. Tolvaptan activated Nrf2 and increased mRNA and protein expression of antioxidant enzyme heme oxygenase-1 (HO-1) in mpkCCD cells and the outer medulla of mouse kidneys. In contrast to BARD, tolvaptan regulated the antioxidant systems via a unique mechanism. Tolvaptan activated the Nrf2/HO-1 antioxidant pathway through phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK). As a result, tolvaptan and BARD could successfully generate synergistic activating effects on Nrf2/HO-1 antioxidant pathway, suggesting that this combination therapy can contribute to the treatment of CKD.
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PMID:Tolvaptan activates the Nrf2/HO-1 antioxidant pathway through PERK phosphorylation. 3123 73