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
-
Insulin Regulation of PEPCK Gene Expression: A Model for Rapid and Reversible Modulation
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Application of Carbon Monoxide for Transplantation
Current Pharmaceutical Biotechnology Aldose Reductase Inhibitors from the Nature
Current Medicinal Chemistry Antidiabetic Activity of Dihydropyrimidine Scaffolds and Structural Insight by Single Crystal X-ray Studies
Medicinal Chemistry Impact of Nutrition Transition and Resulting Morbidities on Economic and Human Development
Current Diabetes Reviews Advanced Glycation End Products (AGEs) and their Involvement in Liver Disease
Current Pharmaceutical Design Novel Strategies to Ameliorate Radiation Injury: A Possible Role for Tetrahydrobiopterin
Current Drug Targets Adult Stem Cells and Skeletal Muscle Regeneration
Current Gene Therapy Contextualizing Genetics for Regional Heart Failure Care
Current Cardiology Reviews Genetic Analysis of Aldose Reductase in Diabetic Complications
Current Medicinal Chemistry Molecular Mechanisms Involved in the Control of Neurohypophyseal Hormones Secretion
Current Pharmaceutical Design Immunophilins are Involved in the Altered Platelet Aggregation Observed in Patients with Type 2 Diabetes Mellitus
Current Medicinal Chemistry The Rationale for Comparative Studies of Accelerated Atherosclerosis in Rheumatic Diseases
Current Vascular Pharmacology Multiple Roles of Fibroblast Growth Factor 21 in Metabolism
Current Pharmaceutical Design Leptin: A Promising Therapeutic Target with Pleiotropic Action Besides Body Weight Regulation
Current Drug Targets Renovascular Hypertension: Lesion Detection, Patient Selection, Treatment Options and Results
Current Hypertension Reviews IgA Nephropathy: Clinical Significance of Urinary Proteins/Polypeptides Characterization
Current Proteomics Growth of Diabetes Research in United Arab Emirates: Current and Future Perspectives
Current Diabetes Reviews Sweet and Sour - Oxidative and Carbonyl Stress in Neurological Disorders
CNS & Neurological Disorders - Drug Targets Application of Pharmacogenomic Approaches in the Study of Drug Response in Complex Diseases
Current Pharmacogenomics