Abstract
An increased oxidative stress may contribute to the development of diabetic nephropathy. We have recently reported that high glucose level stimulated superoxide production through protein kinase C (PKC)-dependent activation of NAD(P)H oxidase in cultured vascular cells. Here we show that 3-hydroxy-3-methylglutaryl CoA reductase inhibitor (statin) attenuates both high glucose level-induced and angiotensin II (Ang II)-induced activation of p42/44 mitogenactivated kinase (MAP kinase) in cultured human mesangial cells through inhibition of NAD(P)H oxidase activity. The intracellular oxidative stress in cultured mesangial cells was evaluated by electron spin resonance (ESR) measurement. MAP kinase activity was evaluated by western blot analysis using anti phospho-specific MAP kinase antibody and anti- ERK-1 antibody. Exposure of the cells to high glucose level (450mg/dl) for 72 hrs significantly increased MAP kinase activity as compared to normal glucose level (100mg/dl). This increase was completely blocked by the treatment of pitavastatin (5x10-7M) as well as a NAD(P)H oxidase inhibitor (diphenylene iodonium, 10-5M) in parallel with the attenuation of oxidative stress. Ang II-induced activation of MAP kinase was also completely blocked by pitavastatin as well as a diphenylene iodonium in parallel with the attenuation of oxidative stress. In conclusion, pitavastatin attenuated high glucose-induced and Ang II- induced MAP kinase activity in mesangial cells through inhibition of NAD(P)H oxidase. Thus, statins may have a potential as a therapeutic tool for early diabetic nephropathy.
Keywords: diabetes, nephropathy, map kinase, nad(p)h oxidase, mesangial cell, oxidative stress
Medicinal Chemistry
Title: Statin Attenuates High Glucose-Induced and Angiotensin II-Induced MAP Kinase Activity Through Inhibition of NAD(P)H Oxidase Activity in Cultured Mesangial Cells
Volume: 1 Issue: 5
Author(s): H. Y. Yu, T. Inoguchi, M. Nakayama, H. Tsubouchi, N. Sato, N. Sonoda, S. Sasaki, K. Kobayashi and H. Nawata
Affiliation:
Keywords: diabetes, nephropathy, map kinase, nad(p)h oxidase, mesangial cell, oxidative stress
Abstract: An increased oxidative stress may contribute to the development of diabetic nephropathy. We have recently reported that high glucose level stimulated superoxide production through protein kinase C (PKC)-dependent activation of NAD(P)H oxidase in cultured vascular cells. Here we show that 3-hydroxy-3-methylglutaryl CoA reductase inhibitor (statin) attenuates both high glucose level-induced and angiotensin II (Ang II)-induced activation of p42/44 mitogenactivated kinase (MAP kinase) in cultured human mesangial cells through inhibition of NAD(P)H oxidase activity. The intracellular oxidative stress in cultured mesangial cells was evaluated by electron spin resonance (ESR) measurement. MAP kinase activity was evaluated by western blot analysis using anti phospho-specific MAP kinase antibody and anti- ERK-1 antibody. Exposure of the cells to high glucose level (450mg/dl) for 72 hrs significantly increased MAP kinase activity as compared to normal glucose level (100mg/dl). This increase was completely blocked by the treatment of pitavastatin (5x10-7M) as well as a NAD(P)H oxidase inhibitor (diphenylene iodonium, 10-5M) in parallel with the attenuation of oxidative stress. Ang II-induced activation of MAP kinase was also completely blocked by pitavastatin as well as a diphenylene iodonium in parallel with the attenuation of oxidative stress. In conclusion, pitavastatin attenuated high glucose-induced and Ang II- induced MAP kinase activity in mesangial cells through inhibition of NAD(P)H oxidase. Thus, statins may have a potential as a therapeutic tool for early diabetic nephropathy.
Export Options
About this article
Cite this article as:
Yu Y. H., Inoguchi T., Nakayama M., Tsubouchi H., Sato N., Sonoda N., Sasaki S., Kobayashi K. and Nawata H., Statin Attenuates High Glucose-Induced and Angiotensin II-Induced MAP Kinase Activity Through Inhibition of NAD(P)H Oxidase Activity in Cultured Mesangial Cells, Medicinal Chemistry 2005; 1 (5) . https://dx.doi.org/10.2174/1573406054864052
DOI https://dx.doi.org/10.2174/1573406054864052 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Assessment of Acute Coronary Syndromes: Focus on Novel Biomarkers
Current Medicinal Chemistry Management of Type-1 and Type-2 Diabetes by Insulin Injections in Diabetology Clinics - A Scientific Research Review
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Implication for Thiazolidinediones (TZDs) as Novel Potential Anti- Inflammatory Drugs
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Mitophagy: A Novel Therapeutic Target for Treating DN
Current Medicinal Chemistry AGE-RAGE System and Carcinogenesis
Current Pharmaceutical Design Synthesis and Evaluation of Thiazolidinedione-Coumarin Adducts as Antidiabetic, Anti-Inflammatory and Antioxidant Agents
Letters in Organic Chemistry Pro-Inflammatory Mechanisms in Diabetic Neuropathy: Focus on the Nuclear Factor Kappa B Pathway
Current Drug Targets Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy
Current Diabetes Reviews Bone Disease in Diabetes
Current Diabetes Reviews Angiotensin Converting Enzyme 2 Activator (DIZE) Modulates Metabolic Profiles in Mice, Decreasing Lipogenesis
Protein & Peptide Letters Effects of Cichorium Intybus Linn on Blood Glucose, Lipid Constituents and Selected Oxidative Stress Parameters in Streptozotocin-Induced Diabetic Rats
Cardiovascular & Hematological Disorders-Drug Targets Protective Effects of Diuretics Against the Development of Cardiovascular Disease in Patients with Chronic Kidney Disease: A Systematic Review
Cardiovascular & Hematological Agents in Medicinal Chemistry The Impact of Omega-3 Fatty Acids on Osteoporosis
Current Pharmaceutical Design Bioprocess and Bioreactor: Next Generation Technology for Production of Potential Plant-based Antidiabetic and Antioxidant Molecules
Current Medicinal Chemistry Hormetic Potential of Sulforaphane (SFN) in Switching Cells’ Fate Towards Survival or Death
Mini-Reviews in Medicinal Chemistry CXCR3-binding Chemokines: Novel Multifunctional Therapeutic Targets
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Medicinal Chemistry of the Epigenetic Diet and Caloric Restriction
Current Medicinal Chemistry Mechanisms of Fetal and Neonatal Renal Impairment by Pharmacologic Inhibition of Angiotensin
Current Medicinal Chemistry From Endothelial Dysfunction to Arterial Stiffness in Diabetes Mellitus
Current Diabetes Reviews Asymmetric Dimethylarginine (ADMA) and Cardiovascular Disease
Vascular Disease Prevention (Discontinued)