Intervention by retinoic acid in oxidative stress-induced apoptosis

Abstract

Retinoic acid (RA) has been considered a propoptotic agent, and little is known about its anti-apoptotic potential. In this article, we describe that RA strongly inhibits hydrogen peroxide (H2O2)-induced apoptosis of mesangial cells by intervention in activator protein 1 (AP-1). Our data showed that: (i) H2O2 induces apoptosis of mesangial cells via the AP-1 pathway; (iii) activation of AP-1 by H2O2 is mediated by the c-Jun N-terminal kinase (JNK)-c-Jun/AP-1 pathway and the extracellular signal-regulated kinase-c-Fos/AP-1 pathway; (iii) RA inhibits H2O2-induced apoptosis via suppression of c-fos/c-jun expression and JNK activation; and (iv) the anti-apoptotic effect of RA is, at least in part, mediated by induction of mitogen-activated protein kinase phosphatase 1.