15-Deoxy-Δ12,14 -prostaglandin J2 induces apoptosis via JNK-mediated mitochondrial pathway in osteoblastic cells

• Published in: Toxicology (Amsterdam) 2008-06, Vol.248 (2), p.121-129
• Main Authors: Lee, Sung Ju, Kim, Myoung Soo, Park, Ji Yeon, Woo, Jae Suk, Kim, Yong Keun
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Emergency; Medical sciences; Toxicology
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2008.03.014

Abstract The cyclopentenone prostaglandin 15-deoxy-Δ12,14 -prostaglandin J2 (15d-PGJ2 ) induces apoptosis in various cell types. However, the underlying mechanism of 15d-PGJ2 -induced apoptosis is not fully understood. The present study was undertaken to determine the molecular mechanism by which 15d-PGJ2 induces apoptosis in MC3T3-E1 mouse osteoblastic cells. 15d-PGJ2 caused a concentration- and time-dependent apoptotic cell death. 15d-PGJ2 induced a transient activation of ERK1/2 and sustained activation of JNK. 15d-PGJ2 -induced cell death was prevented by the JNK inhibitor SP6001, but not by inhibitors of ERK1/2 and p38. JNK activation by 15d-PGJ2 was blocked by antioxidants N -acetylcysteine (NAC) and GSH. 15d-PGJ2 caused ROS generation and 15d-PGJ2 -induced cell death was prevented by antioxidants, suggesting involvement of ROS generation in 15d-PGJ2 -induced cell death. 15d-PGJ2 triggered the mitochondrial apoptotic pathway indicated by enhanced Bax expression, loss of mitochondrial membrane potential, cytochrome c release, and caspase-3 activation. The JNK inhibitor blocked these events induced by 15d-PGJ2 . Taken together, these results suggest that the 15d-PGJ2 induces cell death through the mitochondrial apoptotic pathway dependent of ROS and JNK activation in osteoblastic cells.