Rosiglitazone and PPAR‐γ overexpression protect mitochondrial membrane potential and prevent apoptosis by upregulating anti‐apoptotic Bcl‐2 family proteins

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.

Gross Morphological Study of Gestational Diabetes Mellitus Placenta From South Indian Mothers Compared With Control Placenta

“…These changes collectively can be correlated and supported with the previous findings which state that insulin regulates the fetal and placental development and in any instance if this is altered can reflect on placental morphology [24]. However, both in diet controlled and drug controlled cases of GDM were also found to deliver with large placentas and macrosomic babies [25,26]. The increased baby weight as found in the present study may be one of the consequence of the placental weight and also intrinsic placental dysregulation factors such as glucose transport during pregnancy [27] which is statistically related by strong association with one another and is concordant with other authors [28,29].…”

HO-1 Induced by Cilostazol Protects Against TNF-α-associated Cytotoxicity via a PPAR-γ-dependent Pathway in Human Endothelial Cells

“…The development of new therapeutic agents that preserve the beneficial effects of acute vascular inflammation would have major clinical value. Recently, Wu et al reported that PPAR-γ overexpression protects mitochondrial membrane potential and prevent apoptosis by upregulating the expression of anti-apoptotic Bcl-2 family proteins [38]. In TNF-α-activated endothelial cells, upregulation of PPAR-γ in cells inhibits NF-κB activity [39].…”

Ubiquitination of p53 is Involved in Troglitazone Induced Apoptosis in Cervical Cancer Cells

“…*P P<0.01 versus control groups In this study, Cell counting assay was used to assess the proliferation ability of Hela cells treated with various assay after 24h and 48h (P the inhibition rate of TGZ was remarkably higher than that hours (P that TGZ could inhibit cell proliferation in time-and dose-dependent manner compared with that of the control group (Yoshimura et al, 2003).…”