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

Oxidative Medicine and Cellular Longevity
Dong-dong TangYi-hua Chen

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-induc...Continue Reading

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Citations

May 27, 2017·Oxidative Medicine and Cellular Longevity·Weijin ZhangZhongqing Chen
Aug 21, 2019·Oxidative Medicine and Cellular Longevity·Jordan H CaterAmy R Wyatt

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Methods Mentioned

BETA
Reverse Transcription-PCR
PCR
electrophoresis
Assay
nuclear translocation
confocal microscopy
Fluorescence
flow cytometry

Software Mentioned

Quantity One
SPSS

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