Effects of homocysteine on the binding of extracellular‐superoxide dismutase to the endothelial cell surface

Homocysteine is known to be a risk factor for several vascular diseases. Previously, we found a significant association between plasma homocysteine and plasma extracellular‐superoxide dismutase (EC‐SOD) levels. The binding of EC‐SOD to human and bovine aortic endothelial cell cultures showed significant decreases after incubation with 10 μM homocysteine, whereas the expression of EC‐SOD in fibroblast cell cultures was inhibited with a high concentration (1 mM) of homocysteine. Furthermore, binding of EC‐SOD to heparin immobilized on plates was decreased with homocysteine. These observations suggested that homocysteine decreases the binding of EC‐SOD to vascular endothelial cell surfaces by degradation of endothelial heparan sulfate proteoglycan, which results in a loss of the ability to protect endothelial cell surfaces from oxidative stress.

[1]  K Hirano,et al.  Heparin-induced release of extracellular-superoxide dismutase form (V) to plasma. , 1995, Journal of biochemistry.

[2]  B. Freeman,et al.  Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. , 1991, Archives of biochemistry and biophysics.

[3]  K. Hirano,et al.  Substitution of glycine for arginine-213 in extracellular-superoxide dismutase impairs affinity for heparin and endothelial cell surface. , 1997, The Biochemical journal.

[4]  H. Drexler,et al.  Vascular extracellular superoxide dismutase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. , 2000, Circulation.

[5]  K. Shimada,et al.  Homocysteine, a thrombogenic agent, suppresses anticoagulant heparan sulfate expression in cultured porcine aortic endothelial cells. , 1993, The Journal of clinical investigation.

[6]  K. Hirano,et al.  Quantitative analysis of extracellular-superoxide dismutase in serum and urine by ELISA with monoclonal antibody. , 1992, Clinica chimica acta; international journal of clinical chemistry.

[7]  W. Martin,et al.  Arterial endothelial barrier dysfunction: actions of homocysteine and the hypoxanthine‐xanthine oxidase free radical generating system , 1993, British journal of pharmacology.

[8]  M. Brenowitz,et al.  'Footprinting' proteins on DNA with peroxonitrous acid. , 1993, Nucleic acids research.

[9]  R. Clarke,et al.  Hyperhomocysteinemia: an independent risk factor for vascular disease. , 1991, The New England journal of medicine.

[10]  H. Knapp,et al.  Role of oxidant stress in endothelial dysfunction produced by experimental hyperhomocyst(e)inemia in humans. , 1999, Circulation.

[11]  B. Hultberg,et al.  Higher export rate of homocysteine in a human endothelial cell line than in other human cell lines. , 1998, Biochimica et biophysica acta.

[12]  L. Tibell,et al.  Expression of human extracellular superoxide dismutase in Chinese hamster ovary cells and characterization of the product. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[13]  M. Gordon,et al.  Characterization of human recombinant interleukin 2 binding to heparin and heparan sulfate using an ELISA approach. , 1997, Cytokine.

[14]  M. Law,et al.  Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention. , 1998, Archives of internal medicine.

[15]  S. Marklund,et al.  Non-enzymic glycation of human extracellular superoxide dismutase. , 1991, The Biochemical journal.

[16]  D. Wilcken,et al.  Relationship between total plasma homocysteine, polymorphisms of homocysteine metabolism related enzymes, risk factors and coronary artery disease in the Australian hospital-based population. , 1999, Atherosclerosis.

[17]  G. Starkebaum,et al.  Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine. , 1986, The Journal of clinical investigation.

[18]  T. Podor,et al.  Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells. , 1999, Blood.

[19]  S. Marklund,et al.  Heparin-induced release of extracellular superoxide dismutase to human blood plasma. , 1987, The Biochemical journal.

[20]  D. Wilcken,et al.  Plasma extracellular superoxide dismutase levels in an Australian population with coronary artery disease. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[21]  B. Halliwell.  What nitrates tyrosine? Is nitrotyrosine specific as a biomarker of peroxynitrite formation in vivo? , 1997, FEBS letters.

[22]  S. Marklund,et al.  Human copper-containing superoxide dismutase of high molecular weight. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[23]  T. Oury,et al.  Extracellular superoxide dismutase in vessels and airways of humans and baboons. , 1996, Free radical biology & medicine.

[24]  R. Schlegel,et al.  Promotion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[25]  G. Boers,et al.  Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease. , 1985, The New England journal of medicine.

[26]  D. Wilcken,et al.  Relationship between homocysteine and superoxide dismutase in homocystinuria: possible relevance to cardiovascular risk. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[27]  B. Hultberg,et al.  The cell-damaging effects of low amounts of homocysteine and copper ions in human cell line cultures are caused by oxidative stress. , 1997, Toxicology.

[28]  J. Sadler,et al.  Inhibition of thrombomodulin surface expression and protein C activation by the thrombogenic agent homocysteine. , 1991, The Journal of clinical investigation.

[29]  R. Ross,et al.  Homocystinemia. Vascular injury and arterial thrombosis. , 1974, The New England journal of medicine.

[30]  I. Mcdowell,et al.  Homocysteine and endothelial dysfunction: a link with cardiovascular disease. , 2000, The Journal of nutrition.

[31]  M. Lewis,et al.  Homocysteine-induced inhibition of endothelium-dependent relaxation in rabbit aorta: role for superoxide anions. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[32]  S. Marklund,et al.  The interstitium of the human arterial wall contains very large amounts of extracellular superoxide dismutase. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[33]  S. Marklund.  Expression of extracellular superoxide dismutase by human cell lines. , 1990, The Biochemical journal.

[34]  K. Hirano,et al.  Quantitative and qualitative changes of extracellular-superoxide dismutase in patients with various diseases. , 1994, Clinica chimica acta; international journal of clinical chemistry.

[35]  T. Finkel,et al.  Homocysteine accelerates endothelial cell senescence , 2000, FEBS letters.

[36]  G. Singh,et al.  Homocysteine-dependent Alterations in Mitochondrial Gene Expression, Function and Structure , 1998, The Journal of Biological Chemistry.

[37]  J. Loscalzo,et al.  Homocyst(e)ine Decreases Bioavailable Nitric Oxide by a Mechanism Involving Glutathione Peroxidase* , 1997, The Journal of Biological Chemistry.

[38]  B. Jones,et al.  Homocysteine mediated endothelial cell toxicity and its amelioration. , 1996, Atherosclerosis.

[39]  B. Halliwell,et al.  Thiols and disulphides can aggravate peroxynitrite‐dependent inactivation of α1‐antiproteinase , 1997, FEBS letters.