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

• Published in: Biotechnology letters 2011-09, Vol.33 (9), p.1715-1722
• Main Authors: Song, Guohua, Tian, Hua, Liu, Jia, Zhang, Hongle, Sun, Xuejun, Qin, Shucun
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - metabolism; Aorta - pathology; Applied Microbiology; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biotechnology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Humans; Hydrogen - metabolism; Immunohistochemistry; Life Sciences; Male; Mice; Microbiology; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Original Research Paper; Receptors, Oxidized LDL - antagonists & inhibitors; Receptors, Oxidized LDL - biosynthesis; RNA, Messenger - biosynthesis; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0141-5492; 1573-6776
• DOI: 10.1007/s10529-011-0630-8

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.