15-Deoxy-delta 12,14-prostaglandin J2 induces apoptosis via JNK-mediated mitochondrial pathway in osteoblastic cells.
The cyclopentenone prostaglandin 15-deoxy-delta 12,14-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.
Lee
Sung Ju
SJ
Department of Physiology, College of Medicine, Pusan National University, Pusan 602-739, Republic of Korea.
Kim
Myoung Soo
MS
Park
Ji Yeon
JY
Woo
Jae Suk
JS
Kim
Yong Keun
YK
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007155:Immunologic Factors / Q000633:toxicity*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D047495:PPAR gamma / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D007155:Immunologic Factors; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D048031:JNK Mitogen-Activated Protein Kinases; D015230:Prostaglandin D2