PMID- 24980657
OWN - NLM
STAT- MEDLINE
DCOM- 20151207
LR  - 20181202
IS  - 1477-2566 (Electronic)
IS  - 1465-3249 (Linking)
VI  - 16
IP  - 10
DP  - 2014 Oct
TI  - Autophagy induction is a survival response against oxidative stress in bone 
      marrow-derived mesenchymal stromal cells.
PG  - 1361-70
LID - S1465-3249(14)00563-5 [pii]
LID - 10.1016/j.jcyt.2014.04.006 [doi]
AB  - BACKGROUND AIMS: 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.
CI  - Copyright (c) 2014 International Society for Cellular Therapy. Published by 
      Elsevier Inc. All rights reserved.
FAU - Song, Chunjuan
AU  - Song C
AD  - Department of Physiology and Functional Genomics, College of Medicine, University 
      of Florida, Gainesville, Florida, USA. Electronic address: songcj@ufl.edu.
FAU - Song, Chunjing
AU  - Song C
AD  - Department of Experimental Education, Tianjin University of Traditional Chinese 
      Medicine, Tianjin, China.
FAU - Tong, Fan
AU  - Tong F
AD  - Department of Entomology and Nematology, College of Agricultural and Life 
      Sciences, University of Florida, Gainesville, Florida, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140626
PL  - England
TA  - Cytotherapy
JT  - Cytotherapy
JID - 100895309
RN  - BBX060AN9V (Hydrogen Peroxide)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Autophagy/drug effects/*physiology
MH  - Bone Marrow Cells/cytology/drug effects/*physiology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Hydrogen Peroxide/pharmacology
MH  - Mesenchymal Stem Cells/cytology/drug effects/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxidative Stress/*physiology
MH  - Up-Regulation/drug effects
OTO - NOTNLM
OT  - apoptosis
OT  - autophagy
OT  - bone marrow-derived mesenchymal stromal cell
OT  - oxidative stress
OT  - therapeutic strategy
EDAT- 2014/07/02 06:00
MHDA- 2015/12/15 06:00
CRDT- 2014/07/02 06:00
PHST- 2013/12/12 00:00 [received]
PHST- 2014/03/12 00:00 [revised]
PHST- 2014/04/06 00:00 [accepted]
PHST- 2014/07/02 06:00 [entrez]
PHST- 2014/07/02 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - S1465-3249(14)00563-5 [pii]
AID - 10.1016/j.jcyt.2014.04.006 [doi]
PST - ppublish
SO  - Cytotherapy. 2014 Oct;16(10):1361-70. doi: 10.1016/j.jcyt.2014.04.006. Epub 2014 
      Jun 26.