Role of H(2)O(2)-activated TRPM2 calcium channel in oxidant-induced endothelial injury.
The transient receptor potential (melastatin) 2 (TRPM2), is an oxidant-activated non-selective cation channel that is widely expressed in mammalian tissues including the vascular endothelium. Oxidative stress, through the generation of oxygen metabolites including H(2)O(2), stimulates intracellular ADP-ribose formation which, in turn, opens TRPM2 channels. These channels act as an endogenous redox sensor for mediating oxidative stress/ROS-induced Ca(2+) entry and the subsequent specific Ca(2+)-dependent cellular reactions such as endothelial hyperpermeability and apoptosis. This review summarizes recent findings on the mechanism by which oxidants induce TRPM2 activation, the role of these channels in the signalling vascular endothelial dysfunctions, and the modulation of oxidant-induced TRPM2 activation by PKCalpha and phospho-tyrosine phosphates L1.
Department of Pharmacology, University of Illinois at Chicago, Chicago, Illinois, USA.
Claudie M
CM
Hecquet
Asrar B
AB
Malik
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D020013:Calcium Signaling / Q000187:drug effects*; D002199:Capillary Permeability; D051152:Clusterin / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007249:Inflammation / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects*; D016877:Oxidants / Q000633:toxicity*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011487:Protein Conformation; D051571:Protein Kinase C-alpha / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D013329:Structure-Activity Relationship
D051152:Clusterin; D016877:Oxidants; D000246:Adenosine Diphosphate Ribose; D006861:Hydrogen Peroxide; D051571:Protein Kinase C-alpha; D017027:Protein Tyrosine Phosphatases