Skip to main content

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

Abstract

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.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. 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

    PubMed  Article  CAS  Google Scholar 

  2. Gilmore TD (2006) Introduction to NF-kappaB: players, pathways, perspectives. Oncogene 25(51):6680–6684

    PubMed  Article  CAS  Google Scholar 

  3. 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

    PubMed  Article  CAS  Google Scholar 

  4. 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

    PubMed  Article  CAS  Google Scholar 

  5. 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

    PubMed  CAS  Google Scholar 

  6. 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

    PubMed  Article  CAS  Google Scholar 

  7. Libby P (2002) Inflammation in atherosclerosis. Nature 420(6917):868–874

    PubMed  Article  CAS  Google Scholar 

  8. 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

    PubMed  Article  CAS  Google Scholar 

  9. 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

    PubMed  Article  CAS  Google Scholar 

  10. 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

    PubMed  Article  CAS  Google Scholar 

  11. 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

    PubMed  Article  CAS  Google Scholar 

  12. 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

    PubMed  Article  CAS  Google Scholar 

  13. 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

    PubMed  Article  CAS  Google Scholar 

  14. Perkins ND (2007) Integrating cell-signalling pathways with NF-kappaB and IKK function. Nat Rev Mol Cell Biol 8(1):49–62

    PubMed  Article  CAS  Google Scholar 

  15. 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

    PubMed  Article  CAS  Google Scholar 

  16. 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

    PubMed  Article  Google Scholar 

  17. 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

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by the Taishan Scholars Foundation of Shandong Province and by Special Research Funding of Taishan Medical University.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Shucun Qin.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

Keywords

  • Human umbilical vein endothelial cells
  • H2
  • Lectin-like oxidized LDL receptor-1
  • Nuclear factor κB
  • Tumor necrosis factor-α