Altered Kidney CYP2C and Cyclooxygenase-2 Levels Are Associated with Obesity-Related Albuminuria
| Autor: | David W. Stepp, John D. Imig, Aparajita Dey, John W. Newman, Roger S. Williams, David M. Pollock, Bruce D. Hammock |
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| Rok vydání: | 2004 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Kidney Cortex Endocrinology Diabetes and Metabolism Kidney Glomerulus Medicine (miscellaneous) Type 2 diabetes Kidney Cytochrome P-450 CYP2J2 Nephropathy Excretion Endocrinology Cytochrome P-450 Enzyme System Internal medicine Diabetes mellitus medicine Albuminuria Animals Obesity Cytochrome P450 Family 2 business.industry Microcirculation Body Weight Public Health Environmental and Occupational Health medicine.disease Rats Rats Zucker Isoenzymes Thromboxane B2 medicine.anatomical_structure Blood pressure Diabetes Mellitus Type 2 Steroid 16-alpha-Hydroxylase Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Hypertension Microalbuminuria Aryl Hydrocarbon Hydroxylases medicine.symptom business Food Science |
| Zdroj: | Obesity Research. 12:1278-1289 |
| ISSN: | 1071-7323 |
| DOI: | 10.1038/oby.2004.162 |
| Popis: | DEY, APARAJITA, ROGER S. WILLIAMS, DAVID M. POLLOCK, DAVID W. STEPP, JOHN W. NEWMAN, BRUCE D. HAMMOCK, AND JOHN D. IMIG. Altered Kidney CYP2C and cyclooxygenase-2 levels are associated with obesity-related albuminuria. Obes Res. 2004;12: 1278 –1289. Objective: To determine cytochrome P450 (CYP450) and cyclooxygenase (COX) expression and metabolite regulation and renal damage in the early stages of obesity-related hypertension and diabetes. Research Methods and Procedures: Obese and lean Zucker rats at 10 to 12 weeks of age were studied. Blood pressure was measured in the conscious state using radiotelemetry. Blood glucose levels and body weight were measured periodically. Protein expression of CYP450 and COX enzymes in the kidney cortex, renal microvessels, and glomeruli was studied. The levels of CYP450 and COX metabolites in urine were measured, and urinary albumin excretion, an indicator of kidney damage, was measured. Results: Body weight and blood glucose averaged 432 20 grams and 105 5 mg/dl, respectively, in obese Zucker rats as compared with 320 8 grams and 91 5 mg/dl, respectively, in age-matched 10- to 12-week-old lean Zucker rats. Renal microvascular CYP4A and COX-2 protein levels were increased 2.3- and 17.0-fold, respectively, in obese Zucker rats. The protein expression of CYP2C11 and CYP2C23 was decreased 2.0-fold in renal microvessels isolated from obese Zucker rats when compared with lean Zucker rats. The urinary excretion rate of thromboxane B2 was increased significantly in obese Zucker as compared with lean Zucker rats (22.0 1.8 vs. 13.4 1.0 ng/d). Urinary albumin excretion, an index of kidney damage, was increased in the obese Zucker rat at this early age. Discussion: These results suggest that increased CYP4A and COX-2 protein levels and decreased CYP2C11 and CYP2C23 protein levels occur in association with microalbuminuria during the onset of obesity-related hypertension and type 2 diabetes. |
| Databáze: | OpenAIRE |
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