Intervention by retinoic acid in oxidative stress-induced apoptosis.
Retinoic acid (RA) has been considered a pro-apoptotic agent, and little is known about its anti-apoptotic potential. In this article, we describe that RA strongly inhibits hydrogen peroxide (H(2)O(2))-induced apoptosis of mesangial cells by intervention in activator protein 1 (AP-1). Our data showed that: (i) H(2)O(2) induces apoptosis of mesangial cells via the AP-1 pathway; (iii) activation of AP-1 by H(2)O(2) 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 H(2)O(2)-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.
Kitamura
Masanori
M
Department of Internal Medicine and Institute of Clinical Medicine and Research, Jikei University School of Medicine, Tokyo, Japan.
Ishikawa
Yoshihisa
Y
Moreno-Manzano
Victoria
V
Xu
Qihe
Q
Konta
Tsuneo
T
Lucio-Cazana
Javier
J
Furusu
Akira
A
Nakayama
Kenji
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology*
D016877:Oxidants; D018808:Transcription Factor AP-1; D014212:Tretinoin; D006861:Hydrogen Peroxide