title: Apoptosis of bone marrow mesenchymal stem cells caused by hypoxia/reoxygenation via multiple pathways.
abstract: The irreversible loss of cardiomyocytes remains a key problem to resolve, which forms the cellular basis of cardiac dysfunction. MSCs transplantation brings out a promising potential for myocardial renovation with less limitations. However, this cell transplantation therapy is limited by its poor viability after transplantation. Apoptosis is thought to be the major factor that affects the efficiency of MSCs transplantation. Therefore, exploring the process of apoptosis and the underlying mechanisms of MSCs in the 'harmful' microenvironment is significant for the sake of improving the efficiency of MSCs transplantation therapy. A hypoxia/reoxygenation (H/R) model of MSCs had been established. TUNEL, Hoechst staining and MTT were used for the evaluation of morphological changes, cell viability and apoptosis. Mitochondrial transmembrane potential was detected by JC-1 using the fluorescence microscopy system. The protein expression of cytochrome c, p-ERK, p-AKT, Bcl-2, Bax, p-JNK, HIF-1α and VEGF was assessed for the analysis of protein changes using the Western blot. In our study, H/R insult lead to apoptosis and cell viability lost in a time-dependent manner in MSCs. Multiple pathways were involved in the apoptosis of MSCs, including cytochrome c released from mitochondria to cytosol, mitochondrial transmembrane potential lost. In addition, p-ERK and p-AKT were downregulated, while Bcl-2, p-JNK and VEGF were upregulated. H/R induced the apoptosis in MSCs is through multiple pathways. These multiple pathways will be helpful for understanding and explaining the process and mechanism of apoptosis in MSCs.
authors: Department of Cardiology, Hangzhou Hospital of TCM 453 Ti Yu Chang Road, Hangzhou 310007, China.
authors: Tie-Long
authors: TL
authors: Chen
authors: Department of Cardiology, Hangzhou Hospital of TCM 453 Ti Yu Chang Road, Hangzhou 310007, China.
authors: Guang-Li
authors: GL
authors: Zhu
authors: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University 88 Fang Road, Hangzhou 310009, China.
authors: Jian-An
authors: JA
authors: Wang
authors: Department of Cardiology, Hangzhou Hospital of TCM 453 Ti Yu Chang Road, Hangzhou 310007, China ; Zhejiang University of TCM Hangzhou 310000, China.
authors: Yu
authors: Y
authors: Wang
authors: Department of Cardiology, Hangzhou Hospital of TCM 453 Ti Yu Chang Road, Hangzhou 310007, China.
authors: Xiao-Long
authors: XL
authors: He
authors: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University 88 Fang Road, Hangzhou 310009, China.
authors: Jun
authors: J
authors: Jiang
keywords: Akt; Bax; Bcl-2; ERK; HIF-1α; JNK; MSCs; VEGF; apoptosis; cytochrome c; transmembrane potential