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Oxidative Medicine and Cellular Longevity
Volume 2016 (2016), Article ID 1852340, 14 pages
Research Article

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

Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China

Received 31 July 2015; Revised 18 October 2015; Accepted 10 December 2015

Academic Editor: Shane Thomas

Copyright © 2016 Dong-dong Tang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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