Increased oxidative stress in the streptozotocin-induced diabetic apoE-deficient mouse: Changes in expression of NADPH oxidase subunits and eNOS

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Abstract

Elevated oxidative stress plays a key role in the development of atherosclerosis and endothelial dysfunction in diabetes-associated vascular disease. Glucose-induced changes in the activity of NADPH oxidase and endothelial nitric oxide synthase (eNOS) may result in vascular endothelial cell dysfunction via dysregulation of eNOS and/or changes in the expression of the subunits of NADPH oxidase. In this study, we have investigated whether changes in the expression of the subunits of NADPH oxidase, or eNOS mRNA, can be associated with oxidative stress in the streptozotocin-induced type 1 diabetic apolipoprotein E-deficient (apoE -/-) diabetic mouse. Oxidative stress was assessed in aorta and mesenteric arteries by immunofluorescence labelling with dihydroethidium and levels of NADPH oxidase subunits and eNOS were determined by a real-time polymerase chain reaction protocol. Blood glucose levels and oxidative stress were significantly increased following 4, 8 and 16 weeks after treatment with streptozotocin in both streptozotocin-apoE -/- aorta and mesenteric arteries compared to the time- and age-matched vehicle (citrate buffer)-treated non-diabetic apoE -/-. In the mesenteric arteries the expression of nox4 (4 weeks) and gp91phox (nox2) (8 weeks) subunits of NADPH oxidase from streptozotocin-apoE -/- were enhanced as were eNOS mRNA and protein (P < 0.05). However, only eNOS mRNA and protein remained increased at 16 weeks. These data indicate that increased oxidative stress in the vasculature of streptozotocin-apoE -/- mice is linked to changes in eNOS, superoxide dismutase (SOD) and NADPH oxidase expression.

Original languageEnglish
Pages (from-to)121-128
Number of pages8
JournalEuropean Journal of Pharmacology
Volume561
Issue number1-3
DOIs
Publication statusPublished - 30 Apr 2007
Externally publishedYes

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Nitric Oxide Synthase Type III
NADPH Oxidase
Apolipoproteins E
Streptozocin
Oxidative Stress
Mesenteric Arteries
Messenger RNA
Aorta
Vascular Diseases
Citric Acid
Superoxide Dismutase
Fluorescent Antibody Technique
Blood Glucose
Real-Time Polymerase Chain Reaction
Atherosclerosis
Buffers
Proteins
Endothelial Cells
Glucose

Keywords

  • Diabetes
  • eNOS
  • NADPH oxidase
  • Oxidative stress

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

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title = "Increased oxidative stress in the streptozotocin-induced diabetic apoE-deficient mouse: Changes in expression of NADPH oxidase subunits and eNOS",
abstract = "Elevated oxidative stress plays a key role in the development of atherosclerosis and endothelial dysfunction in diabetes-associated vascular disease. Glucose-induced changes in the activity of NADPH oxidase and endothelial nitric oxide synthase (eNOS) may result in vascular endothelial cell dysfunction via dysregulation of eNOS and/or changes in the expression of the subunits of NADPH oxidase. In this study, we have investigated whether changes in the expression of the subunits of NADPH oxidase, or eNOS mRNA, can be associated with oxidative stress in the streptozotocin-induced type 1 diabetic apolipoprotein E-deficient (apoE -/-) diabetic mouse. Oxidative stress was assessed in aorta and mesenteric arteries by immunofluorescence labelling with dihydroethidium and levels of NADPH oxidase subunits and eNOS were determined by a real-time polymerase chain reaction protocol. Blood glucose levels and oxidative stress were significantly increased following 4, 8 and 16 weeks after treatment with streptozotocin in both streptozotocin-apoE -/- aorta and mesenteric arteries compared to the time- and age-matched vehicle (citrate buffer)-treated non-diabetic apoE -/-. In the mesenteric arteries the expression of nox4 (4 weeks) and gp91phox (nox2) (8 weeks) subunits of NADPH oxidase from streptozotocin-apoE -/- were enhanced as were eNOS mRNA and protein (P < 0.05). However, only eNOS mRNA and protein remained increased at 16 weeks. These data indicate that increased oxidative stress in the vasculature of streptozotocin-apoE -/- mice is linked to changes in eNOS, superoxide dismutase (SOD) and NADPH oxidase expression.",
keywords = "Diabetes, eNOS, NADPH oxidase, Oxidative stress",
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AU - Ding, Hong

AU - Hashem, Michael

AU - Triggle, Christopher

PY - 2007/4/30

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N2 - Elevated oxidative stress plays a key role in the development of atherosclerosis and endothelial dysfunction in diabetes-associated vascular disease. Glucose-induced changes in the activity of NADPH oxidase and endothelial nitric oxide synthase (eNOS) may result in vascular endothelial cell dysfunction via dysregulation of eNOS and/or changes in the expression of the subunits of NADPH oxidase. In this study, we have investigated whether changes in the expression of the subunits of NADPH oxidase, or eNOS mRNA, can be associated with oxidative stress in the streptozotocin-induced type 1 diabetic apolipoprotein E-deficient (apoE -/-) diabetic mouse. Oxidative stress was assessed in aorta and mesenteric arteries by immunofluorescence labelling with dihydroethidium and levels of NADPH oxidase subunits and eNOS were determined by a real-time polymerase chain reaction protocol. Blood glucose levels and oxidative stress were significantly increased following 4, 8 and 16 weeks after treatment with streptozotocin in both streptozotocin-apoE -/- aorta and mesenteric arteries compared to the time- and age-matched vehicle (citrate buffer)-treated non-diabetic apoE -/-. In the mesenteric arteries the expression of nox4 (4 weeks) and gp91phox (nox2) (8 weeks) subunits of NADPH oxidase from streptozotocin-apoE -/- were enhanced as were eNOS mRNA and protein (P < 0.05). However, only eNOS mRNA and protein remained increased at 16 weeks. These data indicate that increased oxidative stress in the vasculature of streptozotocin-apoE -/- mice is linked to changes in eNOS, superoxide dismutase (SOD) and NADPH oxidase expression.

AB - Elevated oxidative stress plays a key role in the development of atherosclerosis and endothelial dysfunction in diabetes-associated vascular disease. Glucose-induced changes in the activity of NADPH oxidase and endothelial nitric oxide synthase (eNOS) may result in vascular endothelial cell dysfunction via dysregulation of eNOS and/or changes in the expression of the subunits of NADPH oxidase. In this study, we have investigated whether changes in the expression of the subunits of NADPH oxidase, or eNOS mRNA, can be associated with oxidative stress in the streptozotocin-induced type 1 diabetic apolipoprotein E-deficient (apoE -/-) diabetic mouse. Oxidative stress was assessed in aorta and mesenteric arteries by immunofluorescence labelling with dihydroethidium and levels of NADPH oxidase subunits and eNOS were determined by a real-time polymerase chain reaction protocol. Blood glucose levels and oxidative stress were significantly increased following 4, 8 and 16 weeks after treatment with streptozotocin in both streptozotocin-apoE -/- aorta and mesenteric arteries compared to the time- and age-matched vehicle (citrate buffer)-treated non-diabetic apoE -/-. In the mesenteric arteries the expression of nox4 (4 weeks) and gp91phox (nox2) (8 weeks) subunits of NADPH oxidase from streptozotocin-apoE -/- were enhanced as were eNOS mRNA and protein (P < 0.05). However, only eNOS mRNA and protein remained increased at 16 weeks. These data indicate that increased oxidative stress in the vasculature of streptozotocin-apoE -/- mice is linked to changes in eNOS, superoxide dismutase (SOD) and NADPH oxidase expression.

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