Cyclosporin A pre-incubation attenuates hypoxia/reoxygenation-induced apoptosis in mesenchymal stem cells.
Although mesenchymal stem cells (MSCs) are being tested for cardiac repair, the majority of transplanted cells undergo apoptosis in the ischaemic heart because of the effects of ischaemia/reperfusion, poor blood supply and other pro-apoptotic factors. Several experimental and clinical studies have suggested that cyclosporin A (CsA) treatment reduces apoptosis in human endothelial cells and neurocytes. However, the effect of CsA on the apoptosis in MSCs is still unclear. In this study, we investigated whether CsA could inhibit hypoxia/ reoxygenation (H/R)-induced apoptosis in MSCs. MSCs pre-incubated with or without CsA were subjected to 6 h of hypoxia followed by 12 h of reoxygenation. Our data showed that pre-incubation with 0.5-5 microM CsA dose-dependently protected the MSCs from H/R injury, as evidenced by decreased apoptosis and increased cell viability. CsA inhibited the H/R-induced translocation of cytochrome c, increased bcl-2 expression and restored mitochondrial membrane potential. CsA also increased the expression of p-BAD. We propose that preincubation MSCs with CsA inhibits MSC apoptosis through the mitochondrial and BAD pathway.
Chen
T L
TL
Department of Cardiology, 2nd Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Wang
J A
JA
Shi
H
H
Gui
C
C
Luo
R H
RH
Xie
X J
XJ
Xiang
M X
MX
Zhang
X
X
Cao
J
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D000860:Hypoxia / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D051025:bcl-Associated Death Protein / Q000378:metabolism
C494821:Bad protein, rat; D050778:NFATC Transcription Factors; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D016572:Cyclosporine; D045304:Cytochromes c; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3