PPARγ REGULATES THE MITOCHONDRIAL DYSFUNCTION IN HUMAN NEURAL STEM CELLS WITH TUMOR NECROSIS FACTOR ALPHA

Peroxisome proliferator-activated receptor gamma (PPAR gamma) belongs to a family of ligand-activated transcription factors, and its ligands are known to control many physiological and pathological conditions. The hypothesis of our study was that the PPAR gamma agonist (rosiglitazone) could mediate tumor necrosis factor alpha (TNF alpha) related to the regulation of human neural stem cells (hNSCs), by which TNF alpha possibly fulfills important roles in neuronal impairment. The results show that PPAR gamma mediates the cell viability of hNSCs via the downregulation of the activity of caspase 3, indicating that this rescue effect of PPAR gamma could improve the reduced levels of two mitochondrial regulators, adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1) in the hNSCs with TNF alpha. The stimulation of mitochondrial function by PPAR gamma was associated with activation of the PPAR coactivator1 alpha (PGC1 alpha) pathway by up-regulation of oxidative defense and mitochondrial systems. The above protective effects appeared to be exerted by a direct activation of the rosiglitazone, because it protected hNSCs from TNF gamma-evoked oxidative stress and mitochondrial deficiency. Here we show that the rosiglitazone protects hNSCs against All-induced apoptosis and promotes cell survival. These findings extend our understanding of the central role of PPAR gamma in TNF alpha-related neuronal impairment, which probably increases risks of neurodegenerative diseases. The anti-inflammatory effects of PPAR gamma in the hNSCs with TNF alpha, and the involved mechanisms were also characterized. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.