H2 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 H2 in endothelial cells. H2 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. H2 inhibited the TNF-α-induced activation of NF-κB and the phosphorylation of IκB-α. Furthermore, H2 inhibited the expression of LOX-1 and the activation of NF-κB in apolipoprotein E knockout mice, an animal model of atherosclerosis. Thus, H2 probably inhibits cytokine-induced LOX-1 gene expression by suppressing NF-κB activation.
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This research was supported by the Taishan Scholars Foundation of Shandong Province and by Special Research Funding of Taishan Medical University.
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Song, G., Tian, H., Liu, J. et al. H2 inhibits TNF-α-induced lectin-like oxidized LDL receptor-1 expression by inhibiting nuclear factor κB activation in endothelial cells. Biotechnol Lett 33, 1715–1722 (2011). https://doi.org/10.1007/s10529-011-0630-8
- Human umbilical vein endothelial cells
- Lectin-like oxidized LDL receptor-1
- Nuclear factor κB
- Tumor necrosis factor-α