Anti-apoptotic Actions of PPAR-γ Against Ischemic Stroke

Abstract

Stroke is a leading cause of adult disability and mortality. Diabetes is a major risk factor for stroke. Patients with diabetes have a higher incidence of stroke and a poorer prognosis after stroke. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a ligand-modulated transcriptional factor and a therapeutic target for treating type II diabetes. It is well-documented that activation of PPAR-gamma can also attenuate postischemic inflammation and damage. In this review, we focus on the newly revealed anti-apoptotic actions of PPAR-gamma against cerebral ischemia. PPAR-gamma, by increasing superoxide dismutase/catalase and decreasing nicotinamide adenine dinucleotide phosphate oxidase levels, attenuated ischemia-induced reactive oxygen species and subsequently alleviated the postischemic degradation of Bcl-2, Bcl-xl, and Akt. The preserved Akt phosphorylated Bad. Meanwhile, PPAR-gamma also promotes the transcription of 14-3-3epsilon. Elevated 14-3-3epsilon binds and sequesters p-Bad and prevents Bad translocation to neutralize the anti-apoptotic function of Bcl-2. This review further supports the notion that PPAR-gamma may serve as a potential therapeutic target for treating ischemic stroke.

Nitro-Oleic Acid Attenuates OGD/R-Triggered Apoptosis in Renal Tubular Cells via Inhibition of Bax Mitochondrial Translocation in a PPAR-γ-Dependent Manner

“…Ligands for PPAR-γ include natural compounds such as eicosanoids, oxidized phospholipids, 15-deoxy-Δ12,14-PGJ2 and drugs such as the thiazolidinedione derivative rosiglitazone [8], and have been reported to ameliorate ischemia and reperfusion injury in a PPAR-γ dependent manner. The PPAR-γ antagonist, bisphenol A diglycidyl ether (BADGE) abolishes the protection afforded by rosiglitazone and 15d-PGJ2 in a rat model of intestinal I/R [49].…”

“…The protective role of PPAR-γ in I/R injury is suggested by data showing that heterozygous PPAR-γ-deficient mice subjected to intestinal I/R suffer more pronounced injury than wild-type control mice [6] and that the PPAR-γ agonist, rosiglitazone, is able to control cell apoptosis and contribute to tissue protection [7,8,9]. Therefore, agents that regulate PPAR-γ activation are being actively pursued.…”

New insights into huperzine A for the treatment of Alzheimer's disease

“…Although the precise molecular target of huperzine A on Aβ-induced mitochondrial dysfunction remains to be clarified, whether and how huperzine A affects above mentioned Aβ-mitochondrion interactions could be a very promising future project. Emerging evidence implies that a ligand-activated nuclear transcription factor, peroxisome proliferator-activated receptor (PPAR), could be a potential pharmacological target against inflammation and brain damage after ischemic injury [45][46][47] , and potent dual PPARα/γ agonist exerted anti-inflammatory and neuroprotective effects [48] . Moreover, similar as mitochondrion, endoplasmic reticulum (ER) is a multifunctional organelle that plays a central role in various malignant events in AD (reviewed by [49] ).…”

Mitochondrial disorders and the eye

“…215 PPARγ agonists also demonstrated a role in neurorecovery following transient ischemic injury. [216][217][218] Given the high energy demand yet poor nutrient storage capability of central nervous system neurons, 219 it is not surprising that regulation of cellular energy is pivotal in the context of mitochondrial dysfunction in disorders of aging and the eye. AMPK is an evolutionary preserved cellular "calorimeter" common to all eukaryotes that acts as a cellular switch to activate catabolic pathways and turns off anabolic pathways.…”