Hypochlorite-Modified Albumin Upregulates ICAM-1 Expression via a MAPK–NF-κB Signaling Cascade: Protective Effects of Apocynin

• Main Authors: Dong-dong Tang, Hong-xin Niu, Fen-fen Peng, Hai-bo Long, Zong-rui Liu, Hao Zhao, Yi-hua Chen
• Format: Article
• Language: English
• Published: Hindawi Limited 2016-01-01
• Series: Oxidative Medicine and Cellular Longevity
• Online Access: http://dx.doi.org/10.1155/2016/1852340
• ISSN: 1942-0900; 1942-0994

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 p38MAPK. 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 p38MAPK), 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 p38MAPK was not blocked by SN50. ERK1/2 phosphorylation was blocked by U0126 but not by SB203580, and p38MAPK 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, p38MAPK, 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 p38MAPK, culminating in the activation of NF-κB and involving NOXs among the upstream signals.