Thiazolidinedione Activation of Peroxisome Proliferator-activated Receptor γ Can Enhance Mitochondrial Potential and Promote Cell Survival

• DOI: 10.1074/jbc.m204279200
• Publication Date: 2002-08-26T14:39:46Z
• Authors: Y. Lynn Wang; Kenneth A. Frauwirth; Shamina M. Rangwala; Mitchell A. Lazar; Craig B. Thompson
• Keywords: Thiazolidinedione; Peroxisome proliferator

Thiazolidinediones (TZDs) are widely used for treatment of type 2 diabetes mellitus. Peroxisome proliferator-activated receptor gamma (PPAR gamma) is the molecular target TZDs and believed to mediate apoptotic effects this class drugs in a variety cell types, including B T lymphocytes. The finding that induce lymphocyte death has raised concerns regarding whether might further impair immune functions diabetics. To address issue, we investigated roles PPAR survival. was up-regulated upon activation. As previously reported, agonists induced dose-dependent manner. However, concentrations TZD needed cause were above those gamma-dependent transcription. Surprisingly, at optimal transcriptional activation, activation protected cells from apoptosis following growth factor withdrawal. survival-enhancing depended on both presence gamma. Measurements mitochondrial potential revealed enhanced ability maintain their potential. These data indicate with can promote survival suggest may potentially augment responses diabetic patients.