title: Protective effect of apelin on cultured rat bone marrow mesenchymal stem cells against apoptosis.
abstract: Bone marrow-derived mesenchymal stem cells (BMSCs) have shown great promise for ischemic tissue repair. However, poor viability of transplanted BMSCs within ischemic tissues has limited their therapeutic potential. Apelin, an endogenous peptide, whose level is elevated following ischemia, has been shown to enhance survival of cardiomyocytes and neuronal cells during ischemia. We hypothesized that apelin-13 protects BMSCs from apoptotic death. In this paper we determined the potential mechanism of apelin-13 effects using cultured BMSCs from adult rats. Apoptosis was induced by the specific apoptotic insult serum deprivation (SD) for up to 36 h. Apoptotic cell death was measured using immunostaining and Western blotting in the presence and absence of apelin-13 (0.1 to 5.0 nM) co-applied during SD exposure. SD-induced apoptosis was significantly reduced by apelin-13 in a concentration-dependent manner. SD-induced mitochondrial depolarization, cytochrome c release, and caspase-3 activation were largely prevented by apelin-13. The apelin-13 anti-apoptotic effects were blocked by inhibiting the MAPK/ERK1/2 and PI3K/Akt signaling pathways. Taken together, our findings indicate that apelin-13 is a survival factor for BMSCs and its anti-apoptotic property may prove to be of therapeutic significance in terms of exploiting BMSC-based transplantation therapy.
authors.affiliation: Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Zeng
authors.forename: Shan Ping
authors.initials: SP
authors.lastname: Yu
authors.forename: Tammi
authors.initials: T
authors.lastname: Taylor
authors.forename: Molly
authors.initials: M
authors.lastname: Ogle
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
mesh_terms: D000818:Animals; D000075244:Apelin Receptors; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D045304:Cytochromes c / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000075244:Apelin Receptors; C491284:Aplnr protein, rat; D016895:Culture Media, Serum-Free; D036341:Intercellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled; C495199:apelin-13 peptide; D045304:Cytochromes c; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D053148:Caspase 3