Heparin-induced release of extracellular superoxide dismutase to human blood plasma

Karlsson, Kurt; Marklund, Stefan L.

doi:10.1042/bj2420055

Cited by 215 publications

(125 citation statements)

References 21 publications

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“…It is present in the circulation in equilibrium between the glycosaminoglycans on the endothelial surface and the plasma phase, and acts as the principal enzymatic scavenger of superoxide in the extracellular space (37,38). The plasma levels of extracellular superoxide dismutase correlate positively with plasma homocysteine levels in homocystinuric patients (39) and in patients with mild hyperhomocysteinemia (40).…”

Section: Inhibition Of Cellular Antioxidant Enzymes By Homocysteinementioning

confidence: 99%

Influence of Hyperhomocysteinemia on the Cellular Redox State – Impact on Homocysteine-Induced Endothelial Dysfunction

Weiss

Heydrick²,

Postea³

et al. 2003

Clinical Chemistry and Laboratory Medicine

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Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis. An increasing body of evidence has implicated oxidative stress as being contributory to homocysteine's deleterious effects on the vasculature. Elevated levels of homocysteine may lead to increased generation of superoxide by a biochemical mechanism involving nitric oxide synthase, and, to a lesser extent, by an increase in the chemical oxidation of homocysteine and other aminothiols in the circulation. The resultant increase in superoxide levels is further amplified by homocysteinedependent alterations in the function of cellular antioxidant enzymes such as cellular glutathione peroxidase or extracellular superoxide dismutase. One direct clinical consequence of elevated vascular superoxide levels is the inactivation of the vasorelaxant messenger nitric oxide, leading to endothelial dysfunction. Scavenging of superoxide anion by either superoxide dismutase or 4,5-dihydroxybenzene 1,3-disulfonate (Tiron) reverses endothelial dysfunction in hyperhomocysteinemic animal models and in isolated aortic rings incubated with homocysteine. Similarly, homocysteine-induced endothelial dysfunction is also reversed by increasing the concentration of the endogenous antioxidant glutathione or overexpressing cellular glutathione peroxidase in animal models of mild hyperhomocysteinemia. Taken together, these findings strongly suggest that the adverse vascular effects of homocysteine are at least partly mediated by oxidative inactivation of nitric oxide.

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Section: Inhibition Of Cellular Antioxidant Enzymes By Homocysteinementioning

confidence: 99%

Influence of Hyperhomocysteinemia on the Cellular Redox State – Impact on Homocysteine-Induced Endothelial Dysfunction

Weiss

Heydrick²,

Postea³

et al. 2003

Clinical Chemistry and Laboratory Medicine

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“…This seems unlikely, however, because the release of EC-SOD by heparin represents a very small proportion of total EC-SOD. 35 Finally, it is possible that bias may have been introduced in the interpretation of our results, because this investigation was not blinded. Blinding was not performed because of the invasive nature of this protocol.…”

Section: Mak and Newton Vitamin C And Ventricular Contractility 829mentioning

confidence: 99%

Vitamin C Augments the Inotropic Response to Dobutamine in Humans With Normal Left Ventricular Function

Mak

Newton

2001

Circulation

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Background-We studied the effect of an antioxidant, the intracoronary infusion of vitamin C, on basal and dobutamine-stimulated left ventricular (LV) contractility. Methods and Results-Nineteen patients with normal ventricular function participated in this study. A micromanometertipped catheter was inserted into the LV. In the experimental group (nϭ10), an infusion catheter was positioned in the left main coronary artery. LV peak ϩdP/dt (LV ϩdP/dt) was measured in response to the intravenous infusion of dobutamine before (Dob) and during (Dobϩvit C) the intracoronary infusion of vitamin C. The intracoronary infusion of vitamin C had no effect on basal LV ϩdP/dt or any other hemodynamic parameter. The infusion of vitamin C augmented the LV ϩdP/dt response to dobutamine by 22Ϯ4% (Dob, 1680Ϯ76 mm Hg/s; Dobϩvit C, 1814Ϯ97 mm Hg/s, PϽ0.01). In the control group (nϭ9), LV ϩdP/dt was measured in response to sequential infusions of dobutamine (Dob, Dob-2) given at the same time intervals as in the experimental group but without the intracoronary infusion of vitamin C. In contrast to the experimental group, no difference in LV ϩdP/dt was observed between the 2 infusions of dobutamine (Dob, 1706Ϯ131 mm Hg/s; Dob-2, 1709Ϯ138 mm Hg/s, PϭNS). Conclusions-The administration of the antioxidant vitamin C augments the inotropic response to dobutamine in humans.This suggests that redox environment contributes to the adrenergic regulation of ventricular contractility.

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“…EC-SOD is heterogenous with regard to binding to heparinSepharose and can be separated into three fractions: A, without affinity; B, with weak affinity; and C, with relatively high affinity (5). Most EC-SOD in the vascular system is apparently bound to endothelial cell surfaces (6). Membranebound heparan sulfate is the likely receptor for the enzyme (K. Karlsson and S.L.M., unpublished data) and EC-SOD fraction C is the form that binds (6).…”

mentioning

confidence: 99%

Isolation and sequence of complementary DNA encoding human extracellular superoxide dismutase.

Hjalmarsson¹,

Marklund²,

Engström³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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226

165

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A complementary DNA (cDNA) clone from a human placenta cDNA library encoding extracellular superoxide dismutase (EC-SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) has been isolated and the nucleotide sequence determined. The cDNA has a very high G+C content. EC-SOD is synthesized with a putative 18-amino acid signal peptide, preceding the 222 amino acids in the mature enzyme, indicating that the enzyme is a secretory protein. The first 95 amino acids of the mature enzyme show no sequence homology with other sequenced proteins and there is one possible N-glycosylation site (Asn-89). The amino acid sequence from residues 96-193 shows strong homology (:50%) with the rinal two-thirds of the sequences of all known eukaryotic CuZn SODs, whereas the homology with the P. leiognathi CuZn SOD is clearly lower. The ligands to Cu and Zn, the cysteines forming the intrasubunit disulfide bridge in the CuZn SODs, and the arginine found in all CuZn SODs in the entrance to the active site can all be identified in EC-SOD. A comparison with bovine CuZn SOD, the three-dimensional structure of which is known, reveals that the homologies occur in the active site and the divergencies are in the part constituting the subunit contact area in CuZn SOD. Amino acid sequence 194-222 in the carboxyl-terminal end of EC-SOD is strongly hydrophilic and contains nine amino acids with a positive charge. This sequence probably confers the affnity of EC-SOD for heparin and heparan sulfate.

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Heparin-induced release of extracellular superoxide dismutase to human blood plasma

Cited by 215 publications

References 21 publications

Influence of Hyperhomocysteinemia on the Cellular Redox State – Impact on Homocysteine-Induced Endothelial Dysfunction

Influence of Hyperhomocysteinemia on the Cellular Redox State – Impact on Homocysteine-Induced Endothelial Dysfunction

Vitamin C Augments the Inotropic Response to Dobutamine in Humans With Normal Left Ventricular Function

Isolation and sequence of complementary DNA encoding human extracellular superoxide dismutase.

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