H2 inhibits TNF-α-induced lectin-like oxidized LDL receptor-1 expression by inhibiting nuclear factor κB activation in endothelial cells

Biotechnol Lett. 2011 Sep;33(9):1715-22. doi: 10.1007/s10529-011-0630-8. Epub 2011 May 5.


H(2) is a therapeutic antioxidant that can reduce oxidative stress. Oxidized low-density lipoprotein, which plays roles in atherosclerosis, may promote endothelial dysfunction by binding the cell-surface receptor LOX-1. LOX-1 expression can be upregulated by various stimuli, including TNF-α. Thus, we aimed to examine whether the upregulation of LOX-1 by different stimuli could be blocked by H(2) in endothelial cells. H(2) significantly abolished the upregulation of LOX-1 by different stimuli, including TNF-α, at the protein and mRNA levels. The TNF-α-induced upregulation of LOX-1 was also attenuated by the NF-κB inhibitor N-acetyl-L-cysteine. H(2) inhibited the TNF-α-induced activation of NF-κB and the phosphorylation of IκB-α. Furthermore, H(2) inhibited the expression of LOX-1 and the activation of NF-κB in apolipoprotein E knockout mice, an animal model of atherosclerosis. Thus, H(2) probably inhibits cytokine-induced LOX-1 gene expression by suppressing NF-κB activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Aorta / pathology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism*
  • Gene Expression / drug effects
  • Humans
  • Hydrogen / metabolism*
  • Immunohistochemistry
  • Male
  • Mice
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • RNA, Messenger / biosynthesis
  • Receptors, Oxidized LDL / antagonists & inhibitors
  • Receptors, Oxidized LDL / biosynthesis*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism*


  • Antioxidants
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Oxidized LDL
  • Tumor Necrosis Factor-alpha
  • Hydrogen