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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.

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Authors+Show Affiliations

Lee SJ
Department of Physiology, College of Medicine, Pusan National University, Pusan 602-739, Republic of Korea.
Kim MS
No affiliation info available
Park JY
No affiliation info available
Woo JS
No affiliation info available
Kim YK
No affiliation info available

MeSH

AnimalsApoptosisCell LineCell SurvivalCytochromes cDose-Response Relationship, DrugImmunologic FactorsJNK Mitogen-Activated Protein KinasesMembrane Potential, MitochondrialMiceMitochondriaOsteoblastsPPAR gammaProstaglandin D2Reactive Oxygen SpeciesSignal Transduction

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 -
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