Vitamin A Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin A, including details on retinol, benefits, dosage, supplements, deficiency, information.

Apoptosis induced by atRA in MEPM cells is mediated through activation of caspase and RAR.

Yu Z, Han J, Lin J, Xiao Y, Zhang X, Li Y

School of Stomatology, Peking University Health Science Center, Beijing, China.

We have previously demonstrated that all-trans retinoic (atRA) induced growth inhibition and apoptosis in mouse embryonic palate mesenchymal cells (MEPM). In the present study, we investigated the molecular mechanisms of atRA-induced apoptosis and its putative action pathway. atRA-induced apoptosis is associated with activation of the initiator caspase-9 and the effector caspase-3, but not of the effector caspase-8. A broad caspase inhibitor (z-VAD-fmk), caspase-9 inhibitor z-LEHD-fmk and caspase-3 inhibitor (z-DEVD-fmk) blocked atRA-induced DNA fragmentation and sub-G1 fraction, but not caspase-8 inhibitor z-IETD-fmk. We further showed that atRA dose-dependently promoted mRNA expression of retinoic acid receptor beta (RAR-beta) and gamma. A weaker increase in RAR-alpha mRNA was seen only at the highest concentration of atRA (5 muM). The pan RAR antagonist, BMS493, completely abrogated atRA-induced DNA fragmentation, Sub-G1 fraction, and caspase-3 activation. Taken together, these findings show that caspase-mediated induction of apoptosis by atRA is an RAR-dependent signaling pathway.

Published 12 January 2006 in Toxicol Sci, 89(2): 504-9.
Full-text of this article is available online (may require subscription).

© 2004-2008 Vitamin A Research Today. All Rights Reserved.