title: KCa3.1 channels mediate the increase of cell migration and proliferation by advanced glycation endproducts in cultured rat vascular smooth muscle cells.
abstract: The mechanisms underlying the involvement of advanced glycation endproducts (AGEs) in diabetic atherosclerosis are not fully understood. The present study was designed to investigate whether intermediate-conductance Ca(2+)-activated K(+) channels (K(Ca)3.1 channels) are involved in migration and proliferation induced by AGEs in cultured rat vascular smooth muscle cells (VSMCs) using approaches of whole-cell patch voltage-clamp, cell proliferation and migration assay, and western blot analysis. It was found that the current density and protein level of K(Ca)3.1 channels were enhanced in cells incubated with AGE-BSA (bovine serum albumin), and the effects were reversed by co-incubation of AGE-BSA with anti-RAGE (anti-receptors of AGEs) antibody. The ERK1/2 inhibitors PD98059 and U0126, the P38-MAPK inhibitors SB203580 and SB202190, or the PI3K inhibitors LY294002 and wortmannin countered the K(Ca)3.1 channel expression by AGE-BSA. In addition, AGE-BAS increased cell migration and proliferation, and the effects were fully reversed with anti-RAGE antibody, the K(Ca)3.1 channel blocker TRAM-34, or K(Ca)3.1 small interfering RNA. These results demonstrate for the first time that AGEs-induced increase of migration and proliferation is related to the upregulation of K(Ca)3.1 channels in rat VMSCs, and the intracellular signals ERK1/2, P38-MAPK and PI3K are involved in the regulation of K(Ca)3.1 channel expression.
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Zhao
authors.forename: Xing-Li
authors.initials: XL
authors.lastname: Su
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Li
authors.forename: Xiu-Ling
authors.initials: XL
authors.lastname: Deng
mesh_terms: D000704:Analysis of Variance; D000730:Androstadienes; D000818:Animals; D015153:Blotting, Western; D002070:Butadienes; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002867:Chromones; D005419:Flavonoids; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D007093:Imidazoles; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D009025:Morpholines; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology*; D009570:Nitriles; D018408:Patch-Clamp Techniques; D011725:Pyridines; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D012710:Serum Albumin, Bovine; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002070:Butadienes; D002867:Chromones; D005419:Flavonoids; D017127:Glycation End Products, Advanced; D007093:Imidazoles; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C491575:Kcnn4 protein, rat; D009025:Morpholines; D009570:Nitriles; D011725:Pyridines; D034741:RNA, Small Interfering; C113580:U 0126; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093642:SB 203580; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin