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

Diabetes Res Clin Pract. 2013 Jun;100(3):368-75. doi: 10.1016/j.diabres.2013.03.036. Epub 2013 Apr 22.

Abstract

Aims: To examine whether overexpression of peroxisome proliferator activated receptor-gamma coactivator-1 alpha (PGC-1α) 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-1α in ASCs using an adenoviral vector encoding green fluorescent protein (GFP) or PGC-1α 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-H2XRos fluorescent probes.

Results: Under conditions of high glucose, hypoxia and serum deprivation, the overexpression of PGC-1α in ASCs decreased apoptosis and led to an increased survival rate. The ASCs modified with PGC-1α produced lower intracellular and mitochondrial ROS. The mitochondrial morphology and structure in the PGC-1α-ASC group remained relatively complete compared with the control group.

Conclusions: These results reveal a crucial protective role for PGC-1α in the treatment of diabetes mellitus and its complications using stem cells therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology*
  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Cells, Cultured
  • Female
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, rat
  • Reactive Oxygen Species
  • Transcription Factors