title: AGE-BSA down-regulates endothelial connexin43 gap junctions.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  AGE-BSA down-regulated Cx43 expression in HAEC, mainly through reduced Cx43 transcription, and the process involved activation of ERK and p38 MAPK.
authors.affiliation: Department of Internal Medicine, Mackay Memorial Hospital, New Taipei City 251, Taiwan.
authors.forename: Chi-Young
authors.initials: CY
authors.lastname: Wang
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Liu
authors.forename: Heng-Ju
authors.initials: HJ
authors.lastname: Chen
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Lin
authors.forename: Hsueh-Hsiao
authors.initials: HH
authors.lastname: Wang
authors.forename: Ta-Chuan
authors.initials: TC
authors.lastname: Hung
authors.forename: Hung-I
authors.initials: HI
authors.lastname: Yeh
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D017629:Gap Junctions / Q000378:metabolism / Q000502:physiology*; D017127:Glycation End Products, Advanced / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D018031:Connexin 43; D005419:Flavonoids; D017127:Glycation End Products, Advanced; D007093:Imidazoles; D011725:Pyridines; D012710:Serum Albumin, Bovine; D048051:p38 Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one