Oxidative Injury Mediated by PECAM

Abstract

Reactive oxygen species, such as H 2 O 2 , can cause damage to endothelial cells. Ji et al. show that H 2 O 2 stimulated the phosphorylation of platelet endothelial cell adhesion molecule (PECAM-1) in endothelial cells (natively expressing PECAM-1) or cells transfected to express PECAM-1. Agents that block nonreceptor tyrosine kinases of the Src family inhibited phosphorylation of PECAM-1. Cells expressing PECAM-1 also responded to H 2 O 2 exposure with the activation of a nonselective cation channel, resulting in an increase in cytosolic calcium concentration. This calcium transient required the presence and phosphorylation of PECAM-1, because the current was not observed in cells lacking PECAM-1, in the presence of antibodies against the PECAM-1 intracellular domain, in the presence of agents that inhibit Src, or in cells expressing a nonphosphorylatable mutant of PECAM-1. Thus, oxidants appear to activate Src, which phosphorylates PECAM-1, which is then able to activate a nonselective cation channel that results in the increase in cytosolic calcium, which can lead to toxicity. This may represent one pathway by which oxidants can produce endothelial cell injury. G. Ji, C. D. O'Brien, M. Feldman, Y. Manevich, P. Lim, J. Sun, S. M. Albelda, M. I. Kotlikoff, PECAM-1 (CD31) regulates a hydrogen peroxide-activated nonselective cation channel in endothelial cells. J. Cell Biol. 157 , 173-184 (2002) [Abstract] [Full Text]