monorden has been researched along with Hyperglycemia* in 1 studies
1 other study(ies) available for monorden and Hyperglycemia
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High glucose-induced IKK-Hsp-90 interaction contributes to endothelial dysfunction.
A decline in the bioavailability of nitric oxide (NO) that causes endothelial dysfunction is a hallmark of diabetes. The availability of NO to the vasculature is regulated by endothelial nitric oxide synthase (eNOS) activity and the involvement of heat shock protein-90 (Hsp-90) in the regulation of eNOS activity has been demonstrated. Hsp-90 has been shown to interact with upstream kinases [inhibitor kappaB kinases (IKK)alpha, beta, and gamma] in nonvascular cells. In this study, we have investigated the interaction of Hsp-90-IKKbeta in endothelial cells under conditions of high glucose (HG) as a possible mechanism that diminishes Hsp-90-eNOS interaction, which could contribute to reduced bioavailability of NO. We report for the first time that IKKbeta interacts with Hsp-90, and this interaction is augmented by HG in vascular endothelial cells. HG also augments transcriptional (3.5 +/- 0.65-fold) and translational (1.97 +/- 0.17-fold) expression as well as the catalytic activity of IKKbeta (2.45 +/- 0.4-fold). Both IKKbeta and eNOS could be coimmunoprecipitated with Hsp-90. Inhibition of Hsp-90 with geldanamycin (2 microM) or Radicicol (20 microM) mitigated (0.45 +/- 0.04-fold and 0.93 +/- 0.16-fold, respectively) HG induced-IKKbeta activity (2.5 +/- 0.42-fold). Blocking of IKKbeta expression by IKK inhibitor II (15 microM wedelolactone) or small interferring RNA (siRNA) improved Hsp-90-eNOS interaction and NO production under conditions of HG. These results illuminate a possible mechanism for the declining eNOS activity reported under conditions of HG. Topics: Animals; Benzoquinones; Cattle; Cells, Cultured; Coumarins; Endothelial Cells; Endothelium, Vascular; Enzyme Induction; Fluorescence Resonance Energy Transfer; Glucose; HSP90 Heat-Shock Proteins; Hyperglycemia; I-kappa B Kinase; Immunoprecipitation; Lactams, Macrocyclic; Macrolides; Nitric Oxide; Nitric Oxide Synthase Type III; Recombinant Fusion Proteins; RNA Interference; RNA, Small Interfering; Time Factors; Transcription, Genetic; Transfection; Two-Hybrid System Techniques | 2009 |