title: Hypochlorite-Modified Albumin Upregulates ICAM-1 Expression via a MAPK-NF-κB Signaling Cascade: Protective Effects of Apocynin.
abstract: Hypochlorite-modified albumin (HOCl-alb) has been linked to endothelial dysfunction, which plays an important role in the development of hypertension, diabetes, and chronic kidney disease. However, whether HOCl-alb induces endothelial dysfunction via vascular inflammation and whether a signaling pathway is involved are unknown and have not been investigated. HOCl-alb was found to upregulate ICAM-1 expression in human umbilical vein endothelial cells (HUVECs) in a time- and dose-dependent manner. HOCl-alb time-dependently phosphorylated ERK1/2 and p38(MAPK). HOCl-alb also activated NF-κB. ICAM-1 expression was dose-dependently inhibited by U0126 (a specific inhibitor of MEK1/2, a signal upstream from ERK1/2), SB203580 (a specific inhibitor of p38(MAPK)), and SN50 (a specific inhibitor of NF-κB). U0126 and SB203580 both counteracted the activation of NF-κB, whereas the phosphorylation of ERK1/2 and p38(MAPK) was not blocked by SN50. ERK1/2 phosphorylation was blocked by U0126 but not by SB203580, and p38(MAPK) activity was reduced by SB203580 but not by U0126. Apocynin, a specific NADPH oxidase (NOX) inhibitor, inhibited ICAM-1 expression and the activity of ERK1/2, p38(MAPK), and NF-κB. These results indicate that HOCl-alb-induced ICAM-1 expression is caused by the activation of a redox-sensitive intracellular signal cascade involving ERK1/2 and p38(MAPK), culminating in the activation of NF-κB and involving NOXs among the upstream signals.
authors.affiliation: Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
authors.forename: Dong-dong
authors.initials: DD
authors.lastname: Tang
authors.affiliation: Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
authors.forename: Hong-xin
authors.initials: HX
authors.lastname: Niu
authors.affiliation: Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
authors.forename: Fen-fen
authors.initials: FF
authors.lastname: Peng
authors.affiliation: Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
authors.forename: Hai-bo
authors.initials: HB
authors.lastname: Long
authors.affiliation: Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
authors.forename: Zong-rui
authors.initials: ZR
authors.lastname: Liu
authors.affiliation: Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
authors.forename: Yi-hua
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000098:Acetophenones / Q000737:chemistry*; D000418:Albumins / Q000737:chemistry*; D042783:Endothelial Cells / Q000166:cytology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006997:Hypochlorous Acid / Q000737:chemistry*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D010766:Phosphorylation; D015398:Signal Transduction; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000098:Acetophenones; D000418:Albumins; C573420:ICAM1 protein, human; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1; D006997:Hypochlorous Acid; C056165:acetovanillone; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases