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)

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

Bats have adapted to many different feeding habits, which are known to induce morphophysiological adaptations in several tissues, especially those particularly involved with absorption, metabolism and excretion. The common vampire bat (Desmodus rotundus) has a very unique diet (blood), which, among other challenges, seems to pose a risk to their kidneys, due to the increased nitrogen excretion imposed by their remarkably high protein meal. Fruit-eating bats (Artibeus lituratus) consume a high carbohydrate diet and may be taken as a suitable species for this dietary comparative study. Here we aimed at investigating the renal morphology and stereology, kidneys antioxidant capacity, and plasma antidiuretic hormone (ADH) concentrations in adult fruit-eating and vampire bats. Sixteen animals were captured and used in this study, being 8 adult males from each species. Our results showed higher morphological standards of glomerular area, volumetric density of glomeruli, and renal somatic index for vampire bats, as well as higher reactive species of oxygen (ROS) production, such as nitric oxide (NO), higher plasma iron reduction ability (FRAP), higher activity of the antioxidant enzyme glutathione-S-transferase (GST) and a higher malondialdehyde production (MDA) in vampires' kidneys, compared to the fruit-eating species. The activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were higher in fruit-eating bats. Plasma ADH concentrations were not different between species. Taken together, the renal morphophysiology conditions presented by vampire bats might be associated with a high demand for nitrogenous products excretion imposed by protein and iron overload. These features may play an important role on preventing protein-overload nephropathy, allowing vampires to survive under such a unique diet.
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PMID:Aspects regarding renal morphophysiology of fruit-eating and vampire bats. 3323 86