We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
GATA-4 protects against hypoxia-induced cardiomyocyte injury: effects on mitochondrial membrane potential.
- Authors
Li, Hong-Xia; Zhou, Ya-Feng; Zhao, Xin; Jiang, Bin; Yang, Xiang-Jun
- Abstract
Our previous studies have suggested that GATA-4 increases the differentiation of bone-marrow-derived mesenchymal stem cells (MSCs) into cardiac phenotypes. This study further investigated whether GATA-4 enhances MSC-mediated cardioprotection following hypoxia. MSCs were harvested from rat bone marrow and transduced with GATA-4 (MSCGATA-4). To mimic ischemic injury, cultured cardiomyocytes (CMs) isolated from neonatal rat ventricles were exposed to hypoxia or were pretreated with concentrated conditioned medium (CdM) from MSCGATA-4 or transduced control MSC (MSCNull) for 16 h before exposure to hypoxic culture conditions (low glucose and low oxygen). Myocyte damage was estimated by annexin-V-PE and TUNEL technique and by lactate dehydrogenase (LDH) release. Cell survival was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium (MTT) uptake. Mitochondrial membrane potential was determined using confocal microscopy. ELISA studies indicated that insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) were significantly increased in MSCGATA-4 compared with MSCNull. Hypoxia-induced apoptosis/cell death was significantly reduced when CMs were co-cultured with MSCGATA-4 in a dual-chamber system. Cell protection mediated by MSCGATA-4 was mimicked by treating CMs with CdM from MSCGATA-4 and abrogated with IGF-1- and VEGF-neutralizing antibodies. MSCGATA-4 protects CMs under hypoxic conditions. The release of IGF-1 and VEGF from MSCGATA-4 is likely to be responsible for protection of CMs.
- Subjects
GATA proteins; HYPOXIA-inducible factors; HEART cells; MITOCHONDRIAL membranes; MESENCHYMAL stem cells; BONE marrow
- Publication
Canadian Journal of Physiology & Pharmacology, 2014, Vol 92, Issue 8, p669
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/cjpp-2014-0009