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15-Deoxy-delta 12,14-prostaglandin J2 induces apoptosis via JNK-mediated mitochondrial pathway in osteoblastic cells.
Toxicology. 2008 Jun 27; 248(2-3):121-9.T

Abstract

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.

Authors+Show Affiliations

Department of Physiology, College of Medicine, Pusan National University, Pusan 602-739, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18450357

Citation

Lee, Sung Ju, et al. "15-Deoxy-delta 12,14-prostaglandin J2 Induces Apoptosis Via JNK-mediated Mitochondrial Pathway in Osteoblastic Cells." Toxicology, vol. 248, no. 2-3, 2008, pp. 121-9.
Lee SJ, Kim MS, Park JY, et al. 15-Deoxy-delta 12,14-prostaglandin J2 induces apoptosis via JNK-mediated mitochondrial pathway in osteoblastic cells. Toxicology. 2008;248(2-3):121-9.
Lee, S. J., Kim, M. S., Park, J. Y., Woo, J. S., & Kim, Y. K. (2008). 15-Deoxy-delta 12,14-prostaglandin J2 induces apoptosis via JNK-mediated mitochondrial pathway in osteoblastic cells. Toxicology, 248(2-3), 121-9. https://doi.org/10.1016/j.tox.2008.03.014
Lee SJ, et al. 15-Deoxy-delta 12,14-prostaglandin J2 Induces Apoptosis Via JNK-mediated Mitochondrial Pathway in Osteoblastic Cells. Toxicology. 2008 Jun 27;248(2-3):121-9. PubMed PMID: 18450357.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 15-Deoxy-delta 12,14-prostaglandin J2 induces apoptosis via JNK-mediated mitochondrial pathway in osteoblastic cells. AU - Lee,Sung Ju, AU - Kim,Myoung Soo, AU - Park,Ji Yeon, AU - Woo,Jae Suk, AU - Kim,Yong Keun, Y1 - 2008/03/27/ PY - 2008/01/17/received PY - 2008/03/17/revised PY - 2008/03/18/accepted PY - 2008/5/3/pubmed PY - 2008/7/18/medline PY - 2008/5/3/entrez SP - 121 EP - 9 JF - Toxicology JO - Toxicology VL - 248 IS - 2-3 N2 - 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. SN - 0300-483X UR - https://www.unboundmedicine.com/medline/citation/18450357/15_Deoxy_delta_1214_prostaglandin_J2_induces_apoptosis_via_JNK_mediated_mitochondrial_pathway_in_osteoblastic_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-483X(08)00140-6 DB - PRIME DP - Unbound Medicine ER -