PGC-1α prevents apoptosis in adipose-derived stem cells by reducing reactive oxygen species production in a diabetic microenvironment

Aims: To examine whether overexpression of peroxisome proliferator activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) can prevent apoptosis in adipose-derived stem cells (ASCs) by reducing reactive oxygen species (ROS) production and enhancing mitochondrial function in a diabetic environment. Methods: After the isolation, expansion and characterisation of rat ASCs, we overexpressed PGC-1 alpha in ASCs using an adenoviral vector encoding green fluorescent protein (GFP) or PGC-1 alpha and tested the apoptotic effect under conditions of high glucose, hypoxia and serum deprivation. The production of intracellular ROS and mitochondrial ROS was evaluated using dihydroethidium and CM-H(2)XRos fluorescent probes. Results: Under conditions of high glucose, hypoxia and serum deprivation, the overexpression of PGC-1 alpha in ASCs decreased apoptosis and led to an increased survival rate. The ASCs modified with PGC-1 alpha produced lower intracellular and mitochondrial ROS. The mitochondrial morphology and structure in the PGC-1 alpha-ASC group remained relatively complete compared with the control group. Conclusions: These results reveal a crucial protective role for PGC-1 alpha in the treatment of diabetes mellitus and its complications using stem cells therapy. (C) 2013 Elsevier Ireland Ltd. All rights reserved.