Manganese-superoxide dismutase in endothelial cells: localization and mechanism of induction

Suzuki, Keiichiro; Tatsumi, Haruyuki; Satoh, S.; Senda, Toshiya; Nakata, Toshiyuki; Fujii, Junichi; Taniguchi, Naoyuki

doi:10.1152/ajpheart.1993.265.4.h1173

Cited by 48 publications

(38 citation statements)

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“…46,47 MnSOD is abundant in endothelial cells relative to other cell types, and may play an important protective role in oxidative stress situations like ischemia and inflammation. 48 MR antagonism promoted MnSOD upregulation early after MI. This effect may account for the reduction in p22 phox expression, once this subunit can be upregulated in a positive feedback by reactive oxygen species generation.…”

Section: Sartorio Et Al Eplerenone and Vascular Dysfunction Early Aftmentioning

confidence: 92%

Mineralocorticoid Receptor Blockade Improves Vasomotor Dysfunction and Vascular Oxidative Stress Early After Myocardial Infarction

Sartório

Fraccarollo²,

Galuppo³

et al. 2007

Hypertension

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Abstract-Mineralocorticoid receptor blockade improves mortality early after myocardial infarction (MI). This study investigated the vascular effects of mineralocorticoid receptor blockade in the early phase postinfarction in rats. Starting immediately after coronary ligation, male Wistar rats were treated with placebo or eplerenone (100 mg/kg/d). After 7 days, hemodynamic assessment was performed and endothelial function was determined. Maximum acetylcholineinduced relaxation was significantly attenuated in aortic rings from rats with heart failure after MI, and ameliorated by eplerenone treatment. Endothelium-independent relaxation by DEA-NONOate was similar among the groups. Endothelial NO synthase phosphorylation was reduced in the aorta of MI rats and restored by eplerenone therapy. Angiotensin I-induced vasoconstriction as well as angiotensin-converting enzyme protein levels were enhanced in aortas from MI placebo rats, and reduced by mineralocorticoid receptor inhibition. Aortic reactive oxygen species formation as well as the expression of the NAD(P)H oxidase subunit p22 phox were increased after MI and normalized in eplerenone treated rats. In conclusion, mineralocorticoid receptor antagonism improved endothelial dysfunction in the early phase post-MI. Underlying mechanisms involve inhibition of vascular angiotensin-converting enzyme upregulation and improvement of endothelial NO synthase-derived NO bioavailability. Key Words: aldosterone Ⅲ acute myocardial infarction Ⅲ endothelial dysfunction Ⅲ oxidative stress C hronic heart failure is accompanied by endothelial dysfunction. 1 Increased production of vascular reactive oxygen species, especially superoxide anion (O 2 Ϫ ), as well as diminished antioxidant defense in heart failure contribute to a reduced bioavailability of NO. 2 The renin angiotensin aldosterone system (RAAS) is markedly activated and displays a central role in heart failure progression. 3,4 Aldosterone synthesis and mineralocorticoid receptors (MR) have been described in the vascular wall. 5,6 Aldosterone stimulates vascular ACE expression/activity and potentiates angiotensin II effects. 7-10 Angiotensin II and aldosterone stimulate vascular O 2 Ϫ production, promoting NO scavenging and reducing its bioavailability. [11][12][13] In healthy subjects, contradictory effects of aldosterone on endothelial function are reported. Farquharson et al 14 showed that intravenous infusion of aldosterone reduced the forearm blood flow response to acetylcholine but did not affect sodium nitroprusside-induced vasodilation, thus inducing acute endothelial dysfunction. Others reported that aldosterone increases forearm blood flow and induces vasodilatation by stimulating NO release through rapid nongenomic effects. 15 In a recent investigation, short-term and chronic aldosterone excess did not affect forearm blood flow, but enhanced the vasodilator response to exogenous NO and improved endothelium-dependent NO-mediated vasodilation in the forearm vasculature of healthy men. 16,17 However, in subjects wit...

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Section: Sartorio Et Al Eplerenone and Vascular Dysfunction Early Aftmentioning

confidence: 92%

Mineralocorticoid Receptor Blockade Improves Vasomotor Dysfunction and Vascular Oxidative Stress Early After Myocardial Infarction

Sartório

Fraccarollo²,

Galuppo³

et al. 2007

Hypertension

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“…Gene transfection was performed using the CELL FECTIN™ reagent (Invitrogen). Human umbilical vein endothelial cells (HUVEC) were isolated as described previously (13), and cultured in MCDB131 medium (Invitrogen) containing 10% of fetal bovine serum, human FGF-2 (10 ng/ml), and antibiotics.…”

Section: Methodsmentioning

confidence: 99%

A Secreted Type of β1,6-N-Acetylglucosaminyltransferase V (GnT-V) Induces Tumor Angiogenesis without Mediation of Glycosylation

Saito

Miyoshi

Sasai

et al. 2002

Journal of Biological Chemistry

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Angiogenesis is the first regulatory step of tumor progression. Herein, we report on some findings that show that ␤1,6-N-acetylglucosaminyltransferase V (GnT-V) functions as an inducer of angiogenesis that has a novel and completely different function from the original function of glycosyltransferase. A secreted type of GnT-V protein itself promoted angiogenesis in vitro and in vivo at physiological concentrations. The highly basic domain of GnT-V induced the release of fibroblast growth factor-2 from heparan sulfate proteoglycan on the cell surface and/or extracellular matrix, leading to angiogenesis. These findings provide some novel information on the relationship between GnT-V and tumor metastasis. The inhibition of GnT-V secretion or its expression represents a novel potential strategy for the inhibition of tumor angiogenesis.Angiogenesis represents an obligatory step in cancer progression (1, 2). A variety of factors, such as fibroblast growth factor-2 (FGF-2), 1 vascular endothelial growth factor (VEGF) and interleukin-8, contribute to tumor growth. The production of these factors and cytokines is controlled by complicated mechanisms, which include increased gene expression, posttranslational modifications, and interactions with the extracellular matrix.Many growth factors and their receptors, some of which play a role in tumor angiogenesis, are glycoproteins. Recent studies employing glycosyltransferase gene manipulation have revealed that changes in the oligosaccharide structure of these receptors bring about alterations in intracellular signaling, thus leading to cellular transformation (3-6). ␤1,6-N-acetylglucosaminyltransferase V (GnT-V or mannoside acetylglucosaminyltransferase 5 (Mgat5)), which catalyzes the formation of ␤1-6 branching on N-glycans, has been proposed as one of the most important glycosyltransferases associated with tumor metastasis (7,8). Furthermore, a recent study of GnT-V-deficient mice indicates that it is essential for tumor metastasis as well as for tumor growth (9).Clinical studies have shown increases in GnT-V activity in breast and hepatocellular carcinomas (10, 11). In human breast cancer cells, a positive correlation was observed between GnT-V activity and tumor size (11). We have found that the expression of GnT-V in human colon cancer tissues was correlated with a poor prognosis and distant metastasis (12). This suggests that GnT-V level should be indicative of a poor prognosis in cases of colorectal cancer. These results strongly suggest that GnT-V plays a pivotal role in tumor malignancy. However, the detailed mechanisms of the regulation via GnT-V with respect to tumor size or metastasis remain unknown.To address this issue, we established GnT-V transfectants and examined the metastatic potentials of these cells. In the course of this study, we found that GnT-V transfectants induced dramatic increase in angiogenic activity. The induction of tumor angiogenesis by GnT-V is thought to be due to 1) increases in the expression/production of angiogenic factors, 2) changes...

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“…101 In endothelial cells, treatment with endotoxin resulted in upregulation of antioxidant enzyme activity, consistent with increases in oxidative stress; [102][103][104] however, the enzymatic source of the ROS was not identified. In phagocytic cells, endotoxin potently induces ROS production by stimulating NADPH oxidase activity.…”

Section: Ros and Inflammationmentioning

confidence: 99%

Potential Role of Endotoxin as a Proinflammatory Mediator of Atherosclerosis

Stoll

Denning

Weintraub

2004

ATVB

260

200

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Abstract-Atherosclerosis is increasingly recognized as a chronic inflammatory disease. Although a variety of inflammatory markers (ie, C-reactive protein) have been associated with atherosclerosis and its consequences, it is important to identify principal mediators of the inflammatory responses. One potentially important source of vascular inflammation in atherosclerosis is bacterial endotoxin. Mutations in Toll-like receptor 4 (TLR-4), an integral component of the endotoxin signaling complex, are fairly common in the Caucasian population and have recently been associated with reduced incidence of atherosclerosis and other cardiovascular diseases in some studies. Moreover, epidemiological studies suggest that endotoxemia at levels as low as 50 pg/mL constitutes a strong risk factor for the development of atherosclerosis. Endotoxin concentrations in this range may be produced by a variety of common subclinical Gram-negative infections. In this article, we outline the main elements of the endotoxin signaling receptor complex that initiates proinflammatory signaling (lipopolysaccharide binding protein [LBP], CD14, TLR-4, and MD-2) and discuss how changes in expression of these molecules may affect proatherogenic responses in the vessel wall. We also describe some of the proinflammatory effects of endotoxin that may be relevant to atherosclerosis, and discuss how serum lipoproteins, especially high-density lipoprotein, may modulate endotoxin-induced inflammatory responses. Further, we discuss recent findings suggesting that the lipid-lowering statins may have an additional protective role in blocking at least some of these proinflammatory signaling pathways. Finally, we discuss species diversity with regard to endotoxin signaling that should be considered when extrapolating experimental data from animal models to humans. I n recent years, there has been an increasing recognition of the link between inflammation and atherosclerosis. [1][2][3][4][5][6][7][8] Although markers of chronic inflammation, such as C-reactive protein, are clearly predictive of clinical atherosclerosis, 9,10 the sources of inflammatory responses, and the mechanisms by which inflammation leads to vascular disease, remain to be elucidated. One potentially important source of inflammation is endotoxin (lipopolysaccharide [LPS]), a unique glycolipid that comprises most of the outer leaflet of the outer wall of Gram-negative bacteria (GNB). [11][12][13][14][15] This complex molecule, found exclusively in GNB, consists of a highly variable carbohydrate portion and a unique lipid A region that is highly conserved across many GNB species. Gram-negative organisms colonize the human gastrointestinal, genitourinary, and respiratory tracts and generate endotoxin not only during overt infections but also in common subclinical or chronic conditions such as periodontitis, sinusitis, bronchitis, or diverticulitis. 16 -18 Even in apparently healthy individuals, endotoxin can be detected in human plasma. The Bruneck study provided the first epidemiological e...

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Manganese-superoxide dismutase in endothelial cells: localization and mechanism of induction

Cited by 48 publications

References 0 publications

Mineralocorticoid Receptor Blockade Improves Vasomotor Dysfunction and Vascular Oxidative Stress Early After Myocardial Infarction

Mineralocorticoid Receptor Blockade Improves Vasomotor Dysfunction and Vascular Oxidative Stress Early After Myocardial Infarction

A Secreted Type of β1,6-N-Acetylglucosaminyltransferase V (GnT-V) Induces Tumor Angiogenesis without Mediation of Glycosylation

Potential Role of Endotoxin as a Proinflammatory Mediator of Atherosclerosis

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