title: Autophagy induction is a survival response against oxidative stress in bone marrow-derived mesenchymal stromal cells.
abstract: OBJECTIVE
  Bone marrow-derived mesenchymal stromal cells (BMSCs) are being extensively investigated as cellular therapeutics for many diseases, including cardiovascular diseases. Although preclinical studies indicated that BMSC transplantation into infarcted hearts improved heart function, there are problems to be resolved, such as the low survival rate of BMSCs during the transplantation process and in the ischemic region with extreme oxidative stress. Autophagy plays pivotal roles in maintaining cellular homeostasis and defending against environmental stresses. However, the precise roles of autophagy in BMSCs under oxidative stress remain largely uncharacterized.
  
  
  METHODS
  BMSCs were treated with H2O2, and autophagic flux was examined by means of microtubule-associated protein 1A/1B-light chain 3 II/I ratio (LC3 II/I), autophagosome formation and p62 expression. Cytotoxicity and cell death assays were performed after co-treatment of BMSCs by autophagy inhibitor (3-methyladenine) or autophagy activator (rapamycin) together with H2O2.
  
  
  RESULTS
  We show that short exposure (1 h) of BMSCs to H2O2 dramatically elevates autophagic flux (2- to 4-fold), whereas 6-h prolonged oxidative treatment reduces autophagy but enhances caspase-3 and caspase-6-associated apoptosis. Furthermore, we show that pre- and co-treatment with rapamycin ameliorates H2O2-induced caspase-3 and caspase-6 activation and cell toxicity but that 3-methyladenine exacerbates H2O2-induced cell apoptotic cell death.
  
  
  CONCLUSIONS
  Our results demonstrate that autophagy is critical for the survival of BMSCs under oxidative conditions. Importantly, we also suggest that the early induction of autophagic flux is possibly a self-defensive mechanism common in oxidant-tolerant cells.
authors: Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, Florida, USA. Electronic address: songcj@ufl.edu.
authors: Chunjuan
authors: C
authors: Song
authors: Department of Experimental Education, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors: Chunjing
authors: C
authors: Song
authors: Department of Entomology and Nematology, College of Agricultural and Life Sciences, University of Florida, Gainesville, Florida, USA.
authors: Fan
authors: F
authors: Tong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006861:Hydrogen Peroxide / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D006861:Hydrogen Peroxide
keywords: apoptosis; autophagy; bone marrow–derived mesenchymal stromal cell; oxidative stress; therapeutic strategy