Heparin protects cultured arterial endothelial cells from damage by toxic oxygen metabolites

Hiebert, Linda M.; Liu, Ji-min

doi:10.1016/0021-9150(90)90129-7

Cited by 71 publications

(34 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The K d of XO binding (6 nM) to endothelial cells is comparable with other macromolecules having specific endothelial binding sites, including lipoprotein lipase, diamine oxidase, and EC-SOD (26 -28). Early evidence that exogenous XO could bind to and damage endothelial cells came from the observations that the addition of heparin to XO-treated cells partially limited oxidative injury by mechanisms that did not include the direct scavenging of reactive species by heparin (29,30). Previous studies supported the concept that the endogenous XOR content of non-rodent vascular cells is too low in specific activity to contribute significantly to oxidative signal transduction events or cell injury (31,32).…”

Section: Binding Of Xo To Other Cell Types-mentioning

confidence: 77%

Binding of Xanthine Oxidase to Vascular Endothelium

Houston

Estévez

Chumley³

et al. 1999

Journal of Biological Chemistry

237

View full text Add to dashboard Cite

Concentrations of up to 1.5 milliunits/ml xanthine oxidase (XO) (1.1 g/ml) are found circulating in plasma during diverse inflammatory events. The saturable, high affinity binding of extracellular XO to vascular endothelium and the effects of cell binding on both XO catalytic activity and differentiated vascular cell function are reported herein. Xanthine oxidase purified from bovine cream bound specifically and with high affinity (K d ‫؍‬ 6 nM) at 4°C to bovine aortic endothelial cells, increasing cell XO specific activity up to 10-fold. Xanthine oxidase-cell binding was not inhibited by serum or albumin and was partially inhibited by the addition of heparin. Pretreatment of endothelial cells with chondroitinase, but not heparinase or heparitinase, diminished endothelial binding by ϳ50%, suggesting association with chondroitin sulfate proteoglycans. Analysis of rates of superoxide production by soluble and cell-bound XO revealed that endothelial binding did not alter the percentage of univalent reduction of oxygen to superoxide. Comparison of the extent of CuZn-SOD inhibition of native and succinoylated cytochrome c reduction by cell-bound XO indicated that XO-dependent superoxide production was occurring in a cell compartment inaccessible to CuZn-SOD. This was further supported by the observation of a shift of exogenously added XO from extracellular binding sites to intracellular compartments, as indicated by both proteasereversible cell binding and immunocytochemical localization studies. Endothelium-bound XO also inhibited nitric oxide-dependent cGMP production by smooth muscle cell co-cultures in an SOD-resistant manner. This data supports the concept that circulating XO can bind to vascular cells, impairing cell function via oxidative mechanisms, and explains how vascular XO activity diminishes vasodilatory responses to acetylcholine in hypercholesterolemic rabbits and atherosclerotic humans. The ubiquity of cell-XO binding and endocytosis as a fundamental mechanism of oxidative tissue injury is also affirmed by the significant extent of XO binding to human vascular endothelial cells, rat lung type 2 alveolar epthelial cells, and fibroblasts.

show abstract

Section: Binding Of Xo To Other Cell Types-mentioning

confidence: 77%

Binding of Xanthine Oxidase to Vascular Endothelium

Houston

Estévez

Chumley³

et al. 1999

Journal of Biological Chemistry

237

View full text Add to dashboard Cite

show abstract

“…However, a plausible mechanism of cellular injury is inhibition of glutathione pathway by high glucose environment. Excessive number of oxygen-free radicals produced by reduced glutathione could play an important role in widespread organ damage in diabetes [8]. In our laboratory, cultured endothelial cells were treated with an inhibitor of glutathione, buthionine sulfoxamine, which showed endothelial cell damage similar to that induced by high glucose [9], thereby supporting glutathione inhibition theory in the pathogenesis of glucose-induced endothelial cell damage.…”

Section: Controversies Affecting Carementioning

confidence: 90%

Diabetes Mellitus: Too Many Controversies Affecting Care

Mandal¹,

Hiebert²

2013

UCMS

View full text Add to dashboard Cite

Diabetes care is in disarray mainly due to a lack of consensus among professionals in the diagnosis and management of diabetes. The most common trend is the use of HbA 1 c (glycosylated hemoglobin) above 6.5% in making the diagnosis of diabetes. Similarly, the most common prescription written for treatment of diabetes is metformin, 500 mg to 1000 mg twice daily. FBG (Fasting blood glucose) above 126 mg/dL is a common accompaniment of HbA 1 c, but 2hPPG (2-h postprandial glucose) or 4-h oral glucose tolerance tests are not included in the diagnosis of diabetes. In the early stage of diabetes or impaired glucose tolerance associated with obesity, FBG or HbA 1 c may be useful, but with rising FBG or HbA 1 c despite dual or triple oral antidiabetic therapy, 2hPPPG becomes the mainstay to determine the severity of diabetes and the need for initiation of insulin therapy. It is needless to underscore that 2hPPG relates to outcome measures such as cardiovascular disorders, nephropathy and death. Thus the cornerstone of therapy when 2hPPG is above 200 mg/dL (≥ 11.1 mmol/L) is insulin with a goal to reduce the risk of complications. There is no or only subtle evidence that oral antidiabetic agents will affect 2hPPG or reduce the risk of complications of diabetes. Therefore, the optimal goal of therapy in diabetes is not limited to merely glycemic control, but the intent of glycemic control which is prevention of diabetes complications.

show abstract

“…Many researchers have already reported that plasma EC-SOD activity is increased by administration of HE in mammals, such as humans, porcine, bovine, canines, cats and mice (4)(5)(6)(7)(8)(9)(10). In this paper, we chose the mouse as an experimental animal to investigate the effects of HE, MHF and MHL on SOD activity in vivo.…”

Section: Discussionmentioning

confidence: 99%