Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Oxidative stress injury to vascular endothelial cells covering the lumen of blood vessels is important in the early development of atherosclerosis. It has been reported that ATP causes the progression of atherosclerosis, but the detailed mechanism has not been understood. In this study, we investigated the effects of ATP on oxidative stress on vascular endothelial cells, the initial process of atherosclerosis, and the involvement of ATP receptors, P2X and P2Y receptors, as molecular mechanisms. We found that ATP enhanced the injury effects of hydrogen peroxide on vascular endothelial cells and that ATP is a potent mediator of the oxidative stress induced by hydrogen peroxide. We found the following results,
(1) ATP suppressed the expression of heme oxygenase-1 (HO-1), a protective factor against oxidative stress.
(2) ATP suppressed the expression of HIF-1α, a regulator of HO-1 expression.
(3) ATP suppressed the induction of HO-1 mRNA expression by hydrogen peroxide treatment.
(4) The P2Y receptor antagonist Suramin abrogated the suppression of HO-1 mRNA expression by ATP and the potentiation of its injury effects by hydrogen peroxide, but not by the P2X receptor antagonist PPADS.
These results suggest that ATP may enhance cytotoxicity by inducing an abnormal response to oxidative stress via P2Y receptors in vascular endothelial cells.
