15-Deoxy-Δ12,14-prostaglandin J2, a specific ligand for peroxisome proliferator-activated receptor-γ, induces neuronal apoptosis
- 1 March 2001
- journal article
- Published by Wolters Kluwer Health in NeuroReport
- Vol. 12 (4) , 839-843
- https://doi.org/10.1097/00001756-200103260-00043
Abstract
Although considerable research has shown a role for peroxisome proliferator-activated receptors (PPAR) in adipose differentiation and in the regulation of inflammation, little is known about its possible functions in neurons. We investigated the role of PPARgamma in primary cultures of cortical neurons and human neuroblastoma SH-SYSY cells. Incubation of cortical neurons with the specific PPARgamma ligand 15-Deoxy-delta12,14-prostaglandin J2 (15d-PGJ2) induced morphological changes including neurite degeneration and nuclear condensation that were consistent with neurons dying by apoptosis. The morphological changes associated with incubation of cortical neurons with 15d-PGJ2 were prevented following pretreatment of neurons with the general caspase inhibitor, Z-VAD. These results highlight a novel role for PPARgamma in neurons and suggest that unwarranted activation of PPARgamma may contribute to the neuronal apoptosis associated with certain neurodegenerative disorders including Alzheimer's disease (AD).Keywords
This publication has 23 references indexed in Scilit:
- Cyclopentenone prostaglandins suppress activation of microglia: Down-regulation of inducible nitric-oxide synthase by 15-deoxy-Δ 12,14 -prostaglandin J 2Proceedings of the National Academy of Sciences, 1999
- Expression of the peroxisome proliferator-activated receptor γ (PPARγ) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoproteinProceedings of the National Academy of Sciences, 1998
- Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein SlimbNature, 1998
- The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activationNature, 1998
- PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS: A Nuclear Receptor Signaling Pathway in Lipid PhysiologyAnnual Review of Cell and Developmental Biology, 1996
- Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult ratEndocrinology, 1996
- A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor γ and promotes adipocyte differentiationCell, 1995
- 15-Deoxy-Δ12,14-Prostaglandin J2 is a ligand for the adipocyte determination factor PPARγCell, 1995
- Peroxisome proliferator-activated receptor (PPAR) gamma: adipose- predominant expression and induction early in adipocyte differentiationEndocrinology, 1994
- Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptorsNature, 1992