Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study investigates whether reactive oxygen species (ROS) are involved in p53 activation, and if they are, which species is responsible for the activation. Our hypothesis is that hydroxyl radical (.OH) functions as a messenger for the activation of this tumor suppressor protein. Human lung epithelial cells (A549) were used to test this hypothesis. Cr(VI) was employed as the source of ROS due to its ability to generate a whole spectrum of ROS inside the cell. Cr(VI) is able to activate p53 by increasing the protein levels and enhancing both the DNA binding activity and transactivation ability of the protein. Increased cellular levels of superoxide radicals (O(2)(-).), hydrogen peroxide (H(2)O(2)), and.OH radicals were detected on the addition of Cr(VI) to the cells. Superoxide dismutase, by enhancing the production of H(2)O(2) from O(2)(-). radicals, increased p53 activity. Catalase, an H(2)O(2) scavenger, eliminated.OH radical generation and inhibited p53 activation. Sodium formate and aspirin,.OH radical scavengers, also suppressed p53 activation. Deferoxamine, a metal chelator, inhibited p53 activation by chelating Cr(V) to make it incapable of generating radicals from H(2)O(2). NADPH, which accelerated the one-electron reduction of Cr(VI) to Cr(V) and increased.OH radical generation, dramatically enhanced p53 activation. Thus.OH radical generated from Cr(VI) reduction in A549 cells is responsible for Cr(VI)-induced p53 activation.
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PMID:The role of hydroxyl radical as a messenger in Cr(VI)-induced p53 activation. 1094 36

Reactive oxygen species (ROS) contribute to many glomerular diseases by targeting mesangial cells. ROS have been shown to regulate expression of many antioxidant enzymes including catalase. The mechanism by which the expression of catalase protein is regulated by ROS is not precisely known. Here we report that increased intracellular ROS level by hydrogen peroxide (H(2)O(2)) reduced the expression of catalase. H(2)O(2) increased phosphorylation of Akt kinase in a dose-dependent and sustained manner with a concomitant increase in the phosphorylation of FoxO1 transcription factor. Further analysis revealed that H(2)O(2) promoted rapid activation of phosphatidylinositol (PI) 3 kinase. The PI 3 kinase inhibitor Ly294002 and expression of tumor suppressor protein PTEN inhibited Akt kinase activity, resulting in the attenuation of FoxO1 phosphorylation and preventing the downregulating effect of H(2)O(2) on catalase protein level. Dominant negative Akt attenuated the inhibitory effect of H(2)O(2) on expression of catalase. Constitutively active FoxO1 increased the expression of catalase. However, dominant negative FoxO1 inhibited catalase protein level. Catalase transcription was reduced by H(2)O(2) treatment. Furthermore, expression of dominant negative Akt and constitutively active FoxO1 increased catalase transcription, respectively. These results demonstrate that ROS downregulate the expression of catalase in mesangial cells by PI 3 kinase/Akt signaling via FoxO1 as a target.
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PMID:Downregulation of catalase by reactive oxygen species via PI 3 kinase/Akt signaling in mesangial cells. 1718 97