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

Dong-dong Tang1, Hong-xin Niu1, Fen-fen Peng1

  • 1Division of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.

Insights

Hypochlorite-modified albumin (HOCl-alb) triggers vascular inflammation by activating ERK1/2 and p38 MAPK pathways, leading to NF-κB activation and increased ICAM-1 expression. This highlights a key signaling cascade in endothelial dysfunction.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Vascular Biology

Background:

  • Hypochlorite-modified albumin (HOCl-alb) is implicated in endothelial dysfunction, a factor in hypertension, diabetes, and chronic kidney disease.
  • The precise mechanisms by which HOCl-alb induces vascular inflammation and the specific signaling pathways involved remain largely unexplored.

Purpose of the Study:

  • To investigate whether HOCl-alb induces endothelial dysfunction through vascular inflammation.
  • To identify the intracellular signaling pathways mediating HOCl-alb-induced endothelial dysfunction.

Main Methods:

  • Human umbilical vein endothelial cells (HUVECs) were treated with HOCl-alb.
  • Expression of ICAM-1, phosphorylation of ERK1/2 and p38(MAPK), and activation of NF-κB were assessed.
  • Specific inhibitors (U0126, SB203580, SN50, Apocynin) were used to elucidate signaling pathways.

Main Results:

  • HOCl-alb upregulated ICAM-1 expression in HUVECs in a time- and dose-dependent manner.
  • HOCl-alb induced phosphorylation of ERK1/2 and p38(MAPK) and activated NF-κB.
  • Inhibitors of ERK1/2, p38(MAPK), and NF-κB, as well as a NADPH oxidase (NOX) inhibitor, blocked HOCl-alb-induced ICAM-1 expression and signaling pathway activation.

Conclusions:

  • HOCl-alb-induced ICAM-1 expression is mediated by a redox-sensitive signaling cascade involving ERK1/2 and p38(MAPK) activation.
  • This cascade culminates in NF-κB activation, contributing to vascular inflammation and endothelial dysfunction.
  • NADPH oxidases (NOXs) are involved in the upstream signaling of this pathway.

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