Back to Search
Start Over
15-Deoxy-delta 12,14-prostaglandin J2 induces apoptosis via JNK-mediated mitochondrial pathway in osteoblastic cells.
- Source :
-
Toxicology [Toxicology] 2008 Jun 27; Vol. 248 (2-3), pp. 121-9. Date of Electronic Publication: 2008 Mar 27. - Publication Year :
- 2008
-
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.
- Subjects :
- Animals
Cell Line
Cell Survival drug effects
Cytochromes c metabolism
Dose-Response Relationship, Drug
Membrane Potential, Mitochondrial drug effects
Mice
Mitochondria metabolism
Osteoblasts metabolism
Osteoblasts pathology
PPAR gamma metabolism
Prostaglandin D2 toxicity
Reactive Oxygen Species metabolism
Signal Transduction
Apoptosis drug effects
Immunologic Factors toxicity
JNK Mitogen-Activated Protein Kinases metabolism
Mitochondria drug effects
Osteoblasts drug effects
Prostaglandin D2 analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0300-483X
- Volume :
- 248
- Issue :
- 2-3
- Database :
- MEDLINE
- Journal :
- Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 18450357
- Full Text :
- https://doi.org/10.1016/j.tox.2008.03.014