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Rosiglitazone and PPAR-gamma overexpression protect mitochondrial membrane potential and prevent apoptosis by upregulating anti-apoptotic Bcl-2 family proteins.
J Cell Physiol. 2009 Jul; 220(1):58-71.JC

Abstract

To determine the involvement of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in cytoprotection, we subjected N2-A cells to oxygen-glucose deprivation followed by reoxygenation (H-R). Following H-R insults, H(2)O(2) production was increased while cell viability declined, which was accompanied by loss of mitochondrial membrane potential (MMP), cytochrome c release, caspases 9 and 3 activation, poly(ADP-ribose)polymerase (PARP) cleavage and apoptosis. Rosiglitazone up to 5 microM protected cell viability, normalized MMP, and prevented apoptotic signals. The protective effect of rosiglitazone was abrogated by GW9662, a PPAR-gamma antagonist, or a specific PPAR-gamma small interference RNA (siRNA) but not a control scRNA. PPAR-gamma overexpression alone was effective in maintaining MMP and preventing apoptosis and its protective effect was also abrogated by PPAR-gamma siRNA or GW9662. To elucidate the mechanism by which PPAR-gamma protects MMP and prevents apoptosis, we analyzed Bcl-2, Bcl-xl, and phosphorylated Bad (p-Bad). H-R suppressed them. Rosiglitazone or PPAR-gamma overexpression restored them via PPAR-gamma. Rosiglitazone or PPAR-gamma overexpression preserved phosphorylated Akt and 3-phosphoinositide-dependent kinase-1 (PDK-1) in a PPAR-gamma dependent manner. These results indicate that ligand-activated PPAR-gamma protects N2-A cells against H-R damage by enhancing Bcl-2/Bcl-xl and maintaining p-Bad via preservation of p-Akt.

Authors+Show Affiliations

Graduate Institute of Life Sciences, National Defense Medical Center; Taipei, Taiwan.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19229877

Citation

Wu, Jui-Sheng, et al. "Rosiglitazone and PPAR-gamma Overexpression Protect Mitochondrial Membrane Potential and Prevent Apoptosis By Upregulating Anti-apoptotic Bcl-2 Family Proteins." Journal of Cellular Physiology, vol. 220, no. 1, 2009, pp. 58-71.
Wu JS, Lin TN, Wu KK. Rosiglitazone and PPAR-gamma overexpression protect mitochondrial membrane potential and prevent apoptosis by upregulating anti-apoptotic Bcl-2 family proteins. J Cell Physiol. 2009;220(1):58-71.
Wu, J. S., Lin, T. N., & Wu, K. K. (2009). Rosiglitazone and PPAR-gamma overexpression protect mitochondrial membrane potential and prevent apoptosis by upregulating anti-apoptotic Bcl-2 family proteins. Journal of Cellular Physiology, 220(1), 58-71. https://doi.org/10.1002/jcp.21730
Wu JS, Lin TN, Wu KK. Rosiglitazone and PPAR-gamma Overexpression Protect Mitochondrial Membrane Potential and Prevent Apoptosis By Upregulating Anti-apoptotic Bcl-2 Family Proteins. J Cell Physiol. 2009;220(1):58-71. PubMed PMID: 19229877.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rosiglitazone and PPAR-gamma overexpression protect mitochondrial membrane potential and prevent apoptosis by upregulating anti-apoptotic Bcl-2 family proteins. AU - Wu,Jui-Sheng, AU - Lin,Teng-Nan, AU - Wu,Kenneth K, PY - 2009/2/21/entrez PY - 2009/2/21/pubmed PY - 2009/5/15/medline SP - 58 EP - 71 JF - Journal of cellular physiology JO - J. Cell. Physiol. VL - 220 IS - 1 N2 - To determine the involvement of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in cytoprotection, we subjected N2-A cells to oxygen-glucose deprivation followed by reoxygenation (H-R). Following H-R insults, H(2)O(2) production was increased while cell viability declined, which was accompanied by loss of mitochondrial membrane potential (MMP), cytochrome c release, caspases 9 and 3 activation, poly(ADP-ribose)polymerase (PARP) cleavage and apoptosis. Rosiglitazone up to 5 microM protected cell viability, normalized MMP, and prevented apoptotic signals. The protective effect of rosiglitazone was abrogated by GW9662, a PPAR-gamma antagonist, or a specific PPAR-gamma small interference RNA (siRNA) but not a control scRNA. PPAR-gamma overexpression alone was effective in maintaining MMP and preventing apoptosis and its protective effect was also abrogated by PPAR-gamma siRNA or GW9662. To elucidate the mechanism by which PPAR-gamma protects MMP and prevents apoptosis, we analyzed Bcl-2, Bcl-xl, and phosphorylated Bad (p-Bad). H-R suppressed them. Rosiglitazone or PPAR-gamma overexpression restored them via PPAR-gamma. Rosiglitazone or PPAR-gamma overexpression preserved phosphorylated Akt and 3-phosphoinositide-dependent kinase-1 (PDK-1) in a PPAR-gamma dependent manner. These results indicate that ligand-activated PPAR-gamma protects N2-A cells against H-R damage by enhancing Bcl-2/Bcl-xl and maintaining p-Bad via preservation of p-Akt. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/19229877/Rosiglitazone_and_PPAR_gamma_overexpression_protect_mitochondrial_membrane_potential_and_prevent_apoptosis_by_upregulating_anti_apoptotic_Bcl_2_family_proteins_ L2 - https://doi.org/10.1002/jcp.21730 DB - PRIME DP - Unbound Medicine ER -