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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Cai J, Kang Z, Liu K, Liu W, Li R, Zhang JH, Luo X, Sun X (2009) Neuroprotective effects of hydrogen saline in neonatal hypoxia-ischemia rat model. Brain Res 1256:129–137
Gilmore TD (2006) Introduction to NF-kappaB: players, pathways, perspectives. Oncogene 25(51):6680–6684
Jersmann HP, Hii CS, Ferrante JV, Ferrante A (2001) Bacterial lipopolysaccharide and tumor necrosis factor alpha synergistically increase expression of human endothelial adhesion molecules through activation of NF-kappaB and p38 mitogen-activated protein kinase signaling pathways. Infect Immun 69(3):1273–1279
Kajiyama S, Hasegawa G, Asano M, Hosoda H, Fukui M, Nakamura N, Kitawaki J, Imai S, Nakano K, Ohta M, Adachi T, Obayashi H, Yoshikawa T (2008) Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res 28(3):137–143
Kume N, Murase T, Moriwaki H, Aoyama T, Sawamura T, Masaki T, Kita T (1998) Inducible expression of lectin-like oxidized LDL receptor-1 in vascular endothelial cells. Circ Res 83(3):322–327
Li L, Sawamura T, Renier G (2004) Glucose enhances human macrophage LOX-1 expression: role for LOX-1 in glucose-induced macrophage foam cell formation. Circ Res 94(7):892–901
Libby P (2002) Inflammation in atherosclerosis. Nature 420(6917):868–874
Mihm S, Ennen J, Pessara U, Kurth R, Droge W (1991) Inhibition of HIV-1 replication and NF-kappa B activity by cysteine and cysteine derivatives. AIDS 5(5):497–503
Minami M, Kume N, Kataoka H, Morimoto M, Hayashida K, Sawamura T, Masaki T, Kita T (2000) Transforming growth factor-beta(1) increases the expression of lectin-like oxidized low-density lipoprotein receptor-1. Biochem Biophys Res Commun 272(2):357–361
Musa H, Meek S, Gautel M, Peddie D, Smith AJ, Peckham M (2006) Targeted homozygous deletion of M-band titin in cardiomyocytes prevents sarcomere formation. J Cell Sci 119(Pt 20):4322–4331
Nagase M, Abe J, Takahashi K, Ando J, Hirose S, Fujita T (1998) Genomic organization and regulation of expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) gene. J Biol Chem 273(50):33702–33707
Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S (2007) Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 13(6):688–694
Ohsawa I, Nishimaki K, Yamagata K, Ishikawa M, Ohta S (2008) Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochem Biophys Res Commun 377(4):1195–1198
Perkins ND (2007) Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 8(1):49–62
Sawamura T, Kume N, Aoyama T, Moriwaki H, Hoshikawa H, Aiba Y, Tanaka T, Miwa S, Katsura Y, Kita T, Masaki T (1997) An endothelial receptor for oxidized low-density lipoprotein. Nature 386(6620):73–77
Shin S, Kwon J, Lee S, Kong H, Lee CK, Cho K, Ha NJ, Kim K (2010) Immunostimulatory Effects of Cordyceps militaris on macrophages through the enhanced production of cytokines via the activation of NF-kappaB. Immune Netw 10(2):55–63
Xu X, Gao X, Potter BJ, Cao JM, Zhang C (2007) Anti-LOX-1 rescues endothelial function in coronary arterioles in atherosclerotic ApoE knockout mice. Arterioscler Thromb Vasc Biol 27(4):871–877
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