Role of TRP channels in oxidative stress.
Increasing evidence suggests a pivotal role of reactive oxygen species (ROS) as well as reactive nitrogen species (RNS) in human pathophysiology. A typical target of ROS/RNS signalling is Ca2+ channels which mediate both long-term as well as acute cellular responses to oxidative stress. We have previously reported that cation channels related to the Drosophila transient receptor potential gene product (TRPC proteins) are likely to serve as redox sensors in the vascular endothelium, and demonstrated that TRPC3 expression is a determinant of the nitric oxide sensitivity of store-operated Ca2+ signalling. Experiments with TRPC species overexpressed in HEK293 cells confirmed that TRPC3 and TRPC4 are able to form redox sensitive cation channels. A key mechanism involved in redox activation of TRPC3 appears to be ROS-induced promotion of protein tyrosine phosphorylation and stimulation of phospholipase C activity. In addition, oxidative stress-induced disruption of caveolin 1-rich lipid raft domains, which interfere with functional TRPC channels, is likely to contribute to redox modulation of TRP proteins and to oxidative stress-induced changes in cellular Ca2+ signalling. Taken together, our data suggest TRPC species serve as a link between cellular redox state and Ca2+ homeostasis. Thus, modulation of these cellular redox sensors may offer unique opportunities for therapeutic interventions.
Groschner
Klaus
K
Department of Pharmacology and Toxicology, Karl-Franzens-University, University of Graz, Universitaetsplatz 2, A -8010 Graz, Austria.
Rosker
Christian
C
Lukas
Michael
M
D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010545:Peroxides / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D050052:TRPC Cation Channels; D010738:Type C Phospholipases / Q000494:pharmacology
C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D007473:Ion Channels; D010545:Peroxides; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D002784:Cholesterol; D012964:Sodium; D010738:Type C Phospholipases; D002118:Calcium