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4 "NAD(P)H oxidase"
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High Glucose and/or Free Fatty Acid Damage Vascular Endothelial Cells via Stimulating of NAD(P)H Oxidase-induced Superoxide Production from Neutrophils.
Sang Soo Kim, Sun Young Kim, Soo Hyung Lee, Yang Ho Kang, In Ju Kim, Yong Ki Kim, Seok Man Son
Korean Diabetes J. 2009;33(2):94-104.   Published online April 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.2.94
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AbstractAbstract PDF
BACKGROUND
Oxidative stress and inflammation are important factors in the pathogenesis of diabetes and contribute to the development of diabetic complications. To understand the mechanisms that cause vascular complications in diabetes, we examined the effects of high glucose and/or free fatty acids on the production of superoxide from neutrophils and their role in endothelial cell damage. METHODS: Human neutrophils were incubated in the media containing 5.5 mM D-glucose, 30 mM D-glucose, 3 nM oleic acid, or 30 microM oleic acid for 1 hour to evaluate superoxide production through NAD(P)H oxidase activation. Human aortic endothelial cells were co-cultured with neutrophils exposed to high glucose and oleic acid. We then measured neutrophil adhesion to endothelial cells, neutrophil activation and superoxide production, neutrophil-mediated endothelial cell cytotoxicity and subunits of neutrophil NAD(P)H oxidase. RESULTS: After 1 hour of incubation with various concentrations of glucose and oleic acid, neutrophil adherence to high glucose and oleic acid-treated endothelial cells was significantly increased compared with adhesion to low glucose and oleic acid-treated endothelial cells. Incubation of neutrophils with glucose and free fatty acids increased superoxide production in a dose-dependent manner. High glucose and oleic acid treatment significantly increased expression of the membrane components of NAD(P)H oxidase of neutrophil (gp91(phox)). Endothelial cells co-cultured with neutrophils exposed to high glucose and oleic acid showed increased cytolysis, which could be prevented by an antioxidant, N-acetylcysteine. CONCLUSION: These results suggest that high glucose and/orfree fatty acidsincrease injury of endothelial cells via stimulating NAD(P)H oxidase-induced superoxide production from neutrophils.
High Glucose Modulates Vascular Smooth Muscle Cell Proliferation Through Activation of PKC-sigma-dependent NAD(P)H oxidase.
Bo Hyun Kim, Chang Won Lee, Jung Lae Park, Yang Ho Kang, In Ju Kim, Yong Ki Kim, Seok Man Son
Korean Diabetes J. 2006;30(6):416-427.   Published online November 1, 2006
DOI: https://doi.org/10.4093/jkda.2006.30.6.416
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  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
Oxidative stress is thought to be one of the causative factors contributing to macrovascular complications in diabetes. However, the mechanisms of development and progression of diabetic vascular complications are poorly understood. We hypothesized that PKC-sigma isozyme contributes to ROS generation and determined their roles in the critical intermediary signaling events in high glucose-induced proliferation of vascular smooth muscle (VSM) cells. METHODS: We treated primary cultured rat aortic smooth muscle cells for 72 hours with medium containing 5.5 mmol/L D-glucose (normal glucose), 30 mmol/L D-glucose (high glucose) or 5.5 mmol/L D-glucose plus 24.5 mmol/L mannitol (osmotic control). We then measured cell number, BrdU incorporation, cell cycle and superoxide production in VSM cells. Immunoblotting of PKC isozymes using phoshospecific antibodies was performed, and PKC activity was also measured. RESULTS: High glucose increased VSM cell number and BrdU incorporation and displayed significantly greater percentages of S and G2/M phases than compared to 5.5 mmol/L glucose and osmotic control. The nitroblue tetrazolium (NBT) staining in high glucose-treated VSM cell was more prominent compared with normal glucose-treated VSM cell, which was significantly inhibited by DPI (10 micrometer), but not by inhibitors for other oxidases. High glucose also markedly increased activity of PKC-sigma isozyme. When VSM cells were treated with rottlerin, a specific inhibitor of PKC-sigma or transfected with PKC-sigma siRNA, NBT staining and NAD(P)H oxidase activity were significantly attenuated in the high glucose-treated VSM cells. Furthermore, inhibition of PKC-sigma markedly decreased VSM cell number by high glucose. CONCLUSION: These results suggest that high glucose-induced VSM cell proliferation is dependent upon activation of PKC-sigma, which may responsible for elevated intracellular ROS production in VSM cells, and this is mediated by NAD(P)H oxidase.

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  • High Glucose and/or Free Fatty Acid Damage Vascular Endothelial Cells via Stimulating of NAD(P)H Oxidase-induced Superoxide Production from Neutrophils
    Sang Soo Kim, Sun Young Kim, Soo Hyung Lee, Yang Ho Kang, In Ju Kim, Yong Ki Kim, Seok Man Son
    Korean Diabetes Journal.2009; 33(2): 94.     CrossRef
The Effect of High Glucose on the Proliferation and Migration of Vascular Smooth Muscle Cells.
Mi Kyoung Kim, Yang Ho Kang, Seok Man Son, In Ju Kim, Yong Ki Kim
Korean Diabetes J. 2004;28(5):407-415.   Published online October 1, 2004
  • 961 View
  • 32 Download
AbstractAbstract PDF
BACKGROUND
Oxidative stress contributes to vascular diseases for patients with diabetes by promoting vascular smooth muscle cell (VSMC) proliferation, monocyte/macrophage infiltration, and vascular tone alteration. As the mechanism of development and progression of diabetic vascular complications is poorly understood, this study was aimed to assess the potential role of hyperglycemia-induced oxidative stress and to determine whether thise oxidative stress is a major factor in hyperglycemia-induced migration and proliferation of VSMCs. METHODS: Rat aortic VSMCs were incubated for 48 hours in either a normal glucose (NG, 5.5 mM) or a high glucose (HG, 30 mM) condition. We then measured the proliferation and migration of VSMCs and the superoxide production. RESULTS: The migration and proliferation of VSMCs incubated under a HG condition were markedly increased compared to the NG condition. Treatment with diphenyleneiodonium (DPI, 10 M) and superoxide dismutase (SOD, 500 U/mL) significantly suppressed the HG-induced migration and proliferation of VSMCs. Superoxide production was significantly increased in the HG condition, and it was markedly decreased after a treatment with DPI and SOD. CONCLUSION: These data suggest that HG-induced VSMC migration and proliferation are related to the production of superoxide anion that is derived from NAD(P)H oxidase.
Mechanism of Impaired Endothelium-dependent Vasodilation in Otsuka Long-Evans Tokushima Fatty (OLETF) Rats .
Kook Jin Chun, Seok Man Son, In Ju Kim, Chi Dae Kim, Seok Dong Yoo, Yong Ki Kim
Korean Diabetes J. 2002;26(1):47-57.   Published online February 1, 2002
  • 853 View
  • 16 Download
AbstractAbstract PDF
BACKGROUND
Impaired vascular endothelium-dependent relaxation and augmented contractile responses have been reported in several long-term animals hyperglycemia models and human diabetic patients. Since oxidative stress has been implicated as a contributor to impaired vascular function, the mechanism of an impaired endothelium-dependent vasodilation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats was investigated. METHODS: This present study was undertaken to characterize both the vascular production and the enzymatic source of the superoxide anion in the type 2 diabetic rats. RESULTS: In the thoracic aortas of OLETF rats, endothelium-dependent relaxation was markedly attenuated compared to that of the control rats (LETO, Long-Evans Tokushima Otsuka) in association with a significant increase in superoxide production (2421.39+/-07.01 nmol/min/mg). There was no difference in eNOS expression between the OLETF rats and LETO rats. The increased production of superoxide anion was significantly attenuated by diphenyleneiodonium (DPI, 10 mol/L), NAD (P)H oxidase inhibitor. In line with these results, studies using various enzyme inhibitors such as DPI, allopurinol, rotenone and L-NMMA suggest that the main source of superoxide anions in the aorta is NAD (P)H oxidase. CONCLUSION: These results suggest that enhanced NAD(P)H oxidase activity and reduced nitric oxide (NO) availability through an interaction between NO and superoxide anion contribute to the impaired endothelium-dependent vasodilation in OLETF rats.

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