Bone marrow (BM)-derived mesenchymal stem cells (MSCs) represent the leading candidate cell for tissue regeneration in the ischemic myocardium. However, the poor survival of stem cells transplanted into the ischemic myocardium presents a major obstacle in stem cell-based therapy. C1q tumor
necrosis factor-related protein 3 (CTRP3) is a newly identified adipokine, similar to adiponectin, with beneficial effects on metabolic regulation. It has been shown to enhance the survival of cardiomyocytes during ischemia, while its expression is reduced following ischemia. In the present
study, we examined the hypothesis that CTRP3 may enhance the survival of MSCs during exposure to hypoxia/serum deprivation (SD), and attempted to elucidate the underlying mechanisms. MSCs were obtained from rat bone marrow and cultured. Apoptosis was induced by hypoxia/SD for up to 24 h
and the apoptotic rates were assessed by flow cytometry. MSC proliferation was measured using a Cell Counting kit-8 assay. The expression levels of Akt, Bcl-2, Bax, cytochrome c and cleaved caspase-3 were detected by western blot analysis. Mitochondrial membrane potential was examined
using a membrane-permeable dye. CTRP3 significantly reduced hypoxia/SD-induced apoptosis in a concentration-dependent manner. The hypoxia/SD-induced decrease in the Bcl-2/Bax ratio and the mitochondrial membrane potential, and the increase in cytochrome c and caspase-3 levels were largely
reversed by CTRP3. The anti-apoptotic effects of CTRP3 were blocked by inhibiting the activation of phosphoinositide 3-kinase (PI3K)/Akt signaling pathway with the PI3K inhibitor, LY294002. In conclusion, CTRP3 is a novel anti-apoptotic adipokine that protects MSCs from hypoxia/SD-induced
apoptosis through the PI3K/Akt signaling pathway.
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Document Type: Research Article
The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Heilongjiang Province, P.R. China
Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P.R. China
Publication date: January 1, 2014
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The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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