Prolyl hydroxylase inhibitor dimethyloxalylglycine enhances mesenchymal stem cell survival
Article first published online: 19 FEB 2009
Copyright © 2009 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 106, Issue 5, pages 903–911, 1 April 2009
How to Cite
Liu, X.-B., Wang, J.-A., Ogle, M. E. and Wei, L. (2009), Prolyl hydroxylase inhibitor dimethyloxalylglycine enhances mesenchymal stem cell survival. J. Cell. Biochem., 106: 903–911. doi: 10.1002/jcb.22064
- Issue published online: 17 MAR 2009
- Article first published online: 19 FEB 2009
- Manuscript Accepted: 18 DEC 2008
- Manuscript Received: 30 MAY 2008
- mesenchymal stem cells;
- PI3K/Akt pathway;
Mesenchymal stem cell (MSC) transplantation is a promising approach in the therapy of ischemic heart or CNS diseases; however, the poor viability of MSCs after transplantation critically limits the efficacy of this new strategy. Prolyl hydroxylase inhibition followed by HIF-1α up-regulation participates in the regulation of apoptosis and cell survival, which have been shown in cancer cells and neurons. The role of prolyl hydroxylase inhibition by dimethyloxalylglycine (DMOG) in regulation of cell survival has not been investigated in MSCs. In the present investigation with MSCs, apoptosis and cell death induced by serum deprivation were assessed by caspase-3 activation and trypan blue staining, respectively. The mitochondrial apoptotic pathway and PI3K/Akt cell survival pathway were evaluated. DMOG significantly attenuated apoptosis and cell death of MSCs, stabilized HIF-1α and induced downstream glucose transport 1 (Glut-1) synthesis. DMOG treatment reduced mitochondrial cytochrome c release, nuclear translocation of apoptosis inducing factor (AIF), and promoted Akt phosphorylation. A specific PI3K inhibitor, wortmannin, blocked Akt phosphorylation and abrogated the beneficial effect of DMOG. These data suggest that the DMOG protection of MSCs may provide a novel approach to promote cell survival during cell stress. J. Cell. Biochem. 106: 903–911, 2009. © 2009 Wiley-Liss, Inc.