| Estradiol Attenuates High Glucose Induced Endothelial Nitrotyrosine: Role for Neuronal Nitric Oxide Synthase. | |
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MedLine Citation:
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PMID: 22135215 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Hyperglycemia in diabetes causes increased oxidative stress in the vascular endothelium with generation of free radicals such as superoxide. Peroxynitrite, a highly reactive species generated from superoxide and nitric oxide (NO) induces pro-inflammatory tyrosine nitration of intracellular proteins under such conditions. The female sex hormone estrogen appears to exert protective effects on the non-diabetic endothelium. However, several studies show reduced vascular protection in women with diabetes, suggesting alterations in estrogen signaling under high glucose. In this study, we examined the endothelial effects of estrogen under increasing glucose levels focusing on nitrotyrosine and peroxynitrite. Human umbilical vein endothelial cells (HUVECs) were incubated with normal (5.5 mM) or high (15.5 or 30.5 mM) glucose prior to addition of estradiol (E2, 1 or 10 nM). Selective NO synthase (NOS) inhibitors were used to determine the role of specific NOS isoforms. Addition of E2 significantly reduced high glucose-induced increase in peroxynitrite and consequently, nitrotyrosine. The superoxide levels were unchanged, suggesting effects on NO generation. Inhibition of neuronal NOS (nNOS) reduced high glucose induced nitrotyrosine, demonstrating a critical role for this enzyme. E2 increased nNOS activity under normal glucose while decreasing it under high glucose as determined by its phosphorylation status. These data show that nNOS contributes to endothelial peroxynitrite and subsequent nitrotyrosine generation under high glucose which can be attenuated by E2 through nNOS inhibition. The altered regulation of nNOS by E2 under high glucose is a potential therapeutic target in women with diabetes. |
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Authors:
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Subhadeep Chakrabarti; Christopher C Cheung; Sandra T Davidge |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-30 |
Journal Detail:
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Title: American journal of physiology. Cell physiology Volume: - ISSN: 1522-1563 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-12-2 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901225 Medline TA: Am J Physiol Cell Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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University of Alberta. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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