Hypochlorite-Modified Albumin Upregulates ICAM-1 Expression via a MAPK–NF-κB Signaling Cascade: Protective Effects of Apocynin. (10th January 2016)

• Record Type: Journal Article
• Authors: Tang, Dong-dong; Niu, Hong-xin; Peng, Fen-fen; Long, Hai-bo; Liu, Zong-rui; Zhao, Hao; Chen, Yi-hua
• Other Names: Thomas Shane Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2016(2016)
• Publication Date: 2016-01-10
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2016/1852340
• Languages: English
• ISSNs: 1942-0900

Abstract

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 andp 38 M A P K . HOCl-alb also activated NF- κ B. 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 ofp 38 M A P K ), and SN50 (a specific inhibitor of NF- κ B). U0126 and SB203580 both counteracted the activation of NF- κ B, whereas the phosphorylation of ERK1/2 andp 38 M A P K was not blocked by SN50. ERK1/2 phosphorylation was blocked by U0126 but not by SB203580, andp 38 M A P K 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, p 38 M A P K, and NF- κ B. 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 andp 38 M A P K, culminating in the activation of NF- κ B and involving NOXs among the upstream signals.