The mechanisms of inhibitory actions of gliclazide on neutrophils–endothelial cells adhesion and surface expression of endothelial adhesion molecules mediated by a high glucose concentration

Itoh, Makoto; Omi, Hitoshi; Okouchi, Masahiro; Imaeda, Kazuo; Shimizu, Manabu; Fukutomi, Tatsuya; Okayama, Naotsuka

doi:10.1016/s1056-8727(01)00219-7

Cited by 28 publications

(18 citation statements)

References 26 publications

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“…Studies from other groups showed a significant increased expression of the adhesion molecules by HG exposure in cultured human umbilical vein endothelial cells and human coronary artery endothelial cells (2,18,29), which is slightly different from the results of our present study. We show only a weak but not significant increase in the expression of ICAM-1 and VCAM-1 by HG (e.g., Fig.…”

Section: Discussioncontrasting

confidence: 99%

“…An interaction of HG and serum factors in the stimulation of adhesion molecule expression most likely exists. In other studies (18,29,31), no information is available on how much serum was included in the HG medium for the cells. In contrast, in our current study, the cells were exposed to HG medium containing a very low serum concentration (1% FCS) to avoid a possible strong interaction between HG and serum factors for the stimulation of endothelial adhesion molecule expression while maintaining the cells in a viable but inactivated situation for 5 days.…”

Section: Discussionmentioning

confidence: 99%

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The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects

Rajapakse¹,

Ming²,

Carvas³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Rajapakse AG, Ming XF, Carvas JM, Yang Z. The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects. Am J Physiol Heart Circ Physiol 296: H815-H822, 2009. First published January 9, 2009 doi:10.1152/ajpheart.00756.2008.-Hexosamine biosynthetic pathway (HBP) accounts for some cardiovascular adverse effects of hyperglycemia. We investigated whether the HBP inhibitor azaserine protects against hyperglycemia-induced endothelial damage dependently of HBP. Human endothelial cells isolated from umbilical veins were exposed either to a high (30.5 mmol/l) or low concentration of glucose (5.5 mmol/l) for 4 days, followed by a stimulation with TNF-␣ (1 ng/ml, 24 h). The blockade of the rate-limiting enzyme glutamine:fructose-6-phosphate amidotransferase inhibited HBP flux and oxidative stress (generation of superoxide and peroxynitrite) under the hyperglycemic condition and prevented the synergistic stimulation of VCAM-1 and ICAM-1 expression by hyperglycemia and TNF-␣. In the cells cultured under a low-glucose condition when no increased HBP flux occurred, azaserine enhanced the manganese-superoxide dismutase (MnSOD) protein level and also inhibited the oxidative stress and the expression of VCAM-1 and ICAM-1 in response to TNF-␣. Moreover, the polyphenol resveratrol inhibited the oxidative stress and adhesion molecule expression and did not decrease the HBP flux under the hyperglycemia condition. In addition, in isolated rat aortas exposed to hyperglycemic buffer for 5 h when no significant HBP flux occurred, azaserine upregulated the MnSOD protein level and prevented decreased endothelium-dependent relaxations to acetylcholine. In conclusion, hyperglycemia independently increases oxidative stress and HBP flux, amplifies endothelial inflammation, and impairs endothelial function mainly through oxidative stress and not the HBP pathway. Azaserine protects against hyperglycemic endothelial damage through its antioxidant effect independently of inhibiting HBP pathway. adhesion molecules; endothelium; glucose; O-linked acetylglusamine; superoxide DIABETES MELLITUS is highly associated with an increased risk of cardiovascular morbidity and mortality (10, 34). Chronic hyperglycemia causes glucotoxicity to vascular cells, particularly the endothelial cells, resulting in an increased incidence of cardiovascular events (7). Clinical and experimental studies provide compelling evidence showing that hyperglycemia is associated with impaired endothelium-dependent relaxations (7) and increased endothelial expression of adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) (20, 31). The decreased endothelial nitric oxide (NO) synthase (eNOS) function and upregulation of the adhesion molecules enhance the adhesion of inflammatory cells onto the endothelium followed by a transmigration of the cells into the subendothelial space, a key early process in atherogenesis (15). Numerous proi...

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects

Rajapakse¹,

Ming²,

Carvas³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…9,10) Incubation of human umbilical vein endothelial cells (HUVEC) in culture media containing high glucose enhances the expression of cell surface adhesion molecules through a process that involves nuclear factor-kB (NF-kB), 11) protein kinase C, [12][13][14] and poly ADP ribose polymerase, 15) although the precise mechanism remains to be elucidated. In a previous report, 16) we demonstrated that glycated human serum albumin enhanced E-selectin expression on HUVEC by NF-kB and activator protein-1 (AP-1) via NADPH oxidase activation.…”

Section: )mentioning

confidence: 99%

“…8) Serum concentrations of soluble adhesion molecules such as soluble endothelial leukocyte adhesion molecule (ELAM-1, E-selectin), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are related to the degree of insulin resistance and hyperglycemia in patients with type 2 diabetes. 9,10) Incubation of human umbilical vein endothelial cells (HUVEC) in culture media containing high glucose enhances the expression of cell surface adhesion molecules through a process that involves nuclear factor-kB (NF-kB), 11) protein kinase C, [12][13][14] and poly ADP ribose polymerase, 15) although the precise mechanism remains to be elucidated. In a previous report, 16) we demonstrated that glycated human serum albumin enhanced E-selectin expression on HUVEC by NF-kB and activator protein-1 (AP-1) via NADPH oxidase activation.…”

Section: Protein O-glcnacylation Is Catalyzed By O-glcnac Transferasementioning

confidence: 99%

Protein O-N-Acetylglucosaminylation Modulates Promoter Activities of Cyclic AMP Response Element and Activator Protein 1 and Enhances E-Selectin Expression on HuH-7 Human Hepatoma Cells

Azuma

Miura

Higai

et al. 2007

Biological & Pharmaceutical Bulletin

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A variety of cytoplasmic and nuclear proteins, including transcription factors, cytoskeletal proteins, nuclear pore proteins, and oncogene products, can be modified on serine and threonine residues by O-linked b-N-acetylglucosamine (OGlcNAc).1,2) This post-translational modification is dynamic and inducible and occurs at sites similar and adjacent to phosphorylation sites that are thought to influence protein functions. Therefore, regulation by O-GlcNAcylation is thought to compete with regulation by phosphorylation/dephosphorylation. Furthermore, nuclear transport of proteins is reported to be regulated by the balance of O-GlcNAcylation and phosphorylation.3) These findings suggest that protein O-GlcNAcylation plays an important role in signal transduction and cellular function. 4,5) Protein O-GlcNAcylation is catalyzed by O-GlcNAc transferase (OGT) using uridine diphosphate (UDP)-GlcNAc as a donor substrate. The transferred O-GlcNAc is reversed by OGlcNAc hexosaminidase (O-GlcNAcase).6) UDP-GlcNAc is generated intracellularly from glucose by the hexosamine biosynthesis pathway, wherein glutamine fructose-6-phosphate amidotransferase (GFAT) is a rate-limiting enzyme. Therefore, protein O-GlcNAcylation is regulated by the cellular levels of OGT, O-GlcNAcase, GFAT, and glucose. 7)Hyperglycemia enhances the levels of UDP-GlcNAc and protein O-GlcNAcylation, and perturbations in the regulation of protein O-GlcNAcylation have been implicated in diabetes mellitus, cancer, and neurodegenerative diseases.8) Serum concentrations of soluble adhesion molecules such as soluble endothelial leukocyte adhesion molecule (ELAM-1, E-selectin), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are related to the degree of insulin resistance and hyperglycemia in patients with type 2 diabetes.9,10) Incubation of human umbilical vein endothelial cells (HUVEC) in culture media containing high glucose enhances the expression of cell surface adhesion molecules through a process that involves nuclear factor-kB (NF-kB), 11) protein kinase C, [12][13][14] and poly ADP ribose polymerase, 15) although the precise mechanism remains to be elucidated. In a previous report, 16) we demonstrated that glycated human serum albumin enhanced E-selectin expression on HUVEC by NF-kB and activator protein-1 (AP-1) via NADPH oxidase activation. In type 2 diabetes and the metabolic syndrome, hepatocellular inflammation by hepatic steatosis was also associated with the development of local and systemic insulin resistance. 17,18) It has been established that pro-inflammatory cytokines such as interleukin-1b (IL-1b) and tumor necrosis factor-a (TNF-a) enhance the expression of these adhesion molecules, although there are different patterns of expression among them.19) The organization of the cytokine-inducible element in the E-selectin expression promotor requires NFkB, activating transcription factor-2 (ATF-2), and high mobility group protein (HMG) I(Y) for induction and these interact as a unit with the basal transcr...

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“…This hypothesis can be supported by many observations which suggest that the activity of oral betacytotropic drugs is pleiotropic and not limited solely to the stimulation of beta cells. They produce many other therapeutically positive effects, among them a decrease in insulin resistance (Almer 1984;Fava et al 2002;Gram et al 1988;Itoh et al 2003;Jennings et al 1992;O'Brien et al 2000). This may also involve the activity of the CGT system.…”

Section: Introductionmentioning

confidence: 99%

Cellular glucose transport and glucotransporter 4 expression as a therapeutic target: clinical and experimental studies

Czech

Piątkiewicz

Tatoń

2009

Arch. Immunol. Ther. Exp.

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Introduction: The normalization of cellular glucose assimilation is the basic aim of metabolic therapy in type 2 diabetes mellitus (T2DM). It requires parallel changes in the process of cellular glucose transport (CGT). Therefore the level of CGT could be regarded as a therapeutic target for oral hypoglycemic drugs in T2DM. To explore this hypothesis, CGT levels before and after sulfonylurea therapy were investigated. Peripheral blood lymphocytes were used as a cell model for testing CGT. Materials and Methods: CGT was assessed by experimental in vitro tests allowing timed comparative observation of the transport process during the incubation of lymphocytes with 2-[ 3 H(G)] glucose under basal conditions and after the addition of sulfonylurea or sulfonylurea plus insulin. The incubation tests were performed at baseline in 28 persons with newly diagnosed, therapy-naive T2DM and in 20 control subjects. In the diabetic patients the tests for CGT were repeated after 3 months of sulfonylurea therapy. The level of glucotransporter 4 (GLUT4) expression was also assessed by flow cytometry before and after the therapy. Results: Before treatment, CGT was significantly lower in the subjects with T2DM. The cells responded to the addition of sulfonylurea by a moderate increase in CGT. This response was augmented by the addition of insulin to sulfonylurea in the culture medium. Conclusions: The three-month therapy with sulfonylurea resulted in a significant increase in CGT in all types of culture tests. This sulfonylurea-related improvement in CGT was associated with a near normalization of GLUT4 expression in the cells.

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The mechanisms of inhibitory actions of gliclazide on neutrophils–endothelial cells adhesion and surface expression of endothelial adhesion molecules mediated by a high glucose concentration

Cited by 28 publications

References 26 publications

The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects

The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects

Protein O-N-Acetylglucosaminylation Modulates Promoter Activities of Cyclic AMP Response Element and Activator Protein 1 and Enhances E-Selectin Expression on HuH-7 Human Hepatoma Cells

Cellular glucose transport and glucotransporter 4 expression as a therapeutic target: clinical and experimental studies

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