AGE-BSA down-regulates endothelial connexin43 gap junctions
1 Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, 250 Road Kuo Kuang, Taichung 402, TAIWAN
2 Institute of Molecular Biology, College of Life Sciences, National Chung Hsing University, 250 Road Kuo Kuang, Taichung 402, TAIWAN
3 Graduate Institute of Biotechnology, National Ping-Tung University of Science and Technology, 1 Road Shuefu, Pingtung 912, TAIWAN
4 Departments of Internal Medicine and Medical Research, Mackay Memorial Hospital, 45 Road Minsheng, New Taipei City 251, TAIWAN
5 Department of Nursing, Mackay Medicine, Nursing and Management College, 92 Road Shengjing, Taipei 112, TAIWAN
6 Department of Medicine, Mackay Medical College, 46 Road Zhongzheng, New Taipei City 252, TAIWAN
BMC Cell Biology 2011, 12:19 doi:10.1186/1471-2121-12-19Published: 16 May 2011
Advanced glycation end products generated in the circulation of diabetic patients were reported to affect the function of vascular wall. We examined the effects of advanced glycation end products-bovine serum albumin (AGE-BSA) on endothelial connexin43 (Cx43) expression and gap-junction communication.
In human aortic endothelial cells (HAEC) treated with a series concentrations of AGE-BSA (0-500 μg/ml) for 24 and 48 hours, Cx43 transcript and Cx43 protein were reduced in a dose dependent manner. In addition, gap-junction communication was reduced. To clarify the mechanisms underlying the down-regulation, MAPKs pathways in HAEC were examined. Both a MEK1 inhibitor (PD98059) and a p38 MAPK inhibitor (SB203580) significantly reversed the reductions of Cx43 mRNA and protein induced by AGE-BSA. Consistently, phosphorylation of ERK and p38 MAPK was enhanced in response to exposure to AGE-BSA. However, all reversions of down-regulated Cx43 by inhibitors did not restore the functional gap-junction communication.
AGE-BSA down-regulated Cx43 expression in HAEC, mainly through reduced Cx43 transcription, and the process involved activation of ERK and p38 MAPK.