title: Cadmium induces vascular permeability via activation of the p38 MAPK pathway.
abstract: The vasculature of various organs is a targeted by the environmental toxin, cadmium (Cd). However, mechanisms leading to pathological conditions are poorly understood. In the present study, we examined the effect of cadmium chloride (CdCl2) on human umbilical vein endothelial cells (HUVECs). At 4 μM, CdCl2 induced a hyper-permeability defect in HUVECs, but not the inhibition of cell growth up to 24h. This effect of CdCl2 was dependent on the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. The p38 MAPK inhibitor SB203850 suppressed the CdCl2-induced alteration in trans-endothelial electrical resistance in HUVEC monolayers, a model measurement of vascular endothelial barrier integrity. SB203850 also inhibited the Cd-induced membrane dissociation of vascular endothelial (VE) cadherin and β-catenin, the important components of the adherens junctional complex. In addition, SB203850 reduces the Cd-induced expression and secretion of tumor necrosis factor α (TNF-α). Taken together, our findings suggest that Cd induces vascular hyper-permeability and disruption of endothelial barrier integrity through stimulation of p38 MAPK signaling.
authors.affiliation: Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, China.
authors.forename: Fengyun
authors.initials: F
authors.lastname: Dong
authors.affiliation: Department of Cardiology, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong 250021, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
authors.affiliation: Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, China.
authors.forename: Yinglong
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, China.
authors.forename: Enkui
authors.initials: E
authors.lastname: Hao
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, China.
authors.forename: Suhua
authors.initials: S
authors.lastname: Yan
authors.affiliation: G.W. Hooper Research Foundation, University of California at San Francisco, 513 Parnassus Ave., HSW1501, San Francisco, CA 94143-0552, USA.
authors.forename: Thaddeus D
authors.initials: TD
authors.lastname: Allen
authors.affiliation: Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, China. Electronic address: ju.liu@sdu.edu.cn.
authors.forename: Ju
authors.initials: J
authors.lastname: Liu
mesh_terms: D002104:Cadmium / Q000633:toxicity*; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D002104:Cadmium; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Cadmium; Endothelial cells; Permeability; p38 MAPK