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Nicotine worsens the severity of nephropathy in diabetic mice: implications for the progression of kidney disease in smokers

wanyair 添加于 2010-10-31 09:20 | 1509 次阅读 | 0 个评论

作者
Hua P, Feng W, Ji S, Raij L, Jaimes EA
摘要
Epidemiological studies have established the role of cigarette smoking as a risk factor in the progression of chronic kidney disease, including diabetic nephropathy. We have previously reported that nicotine promotes mesangial cell proliferation and hypertrophy via activation of nonneuronal nicotinic acetylcholine receptors and that nicotine worsens renal injury in a model of acute glomerulonephritis (Jaimes E, Tian RX, Raij L. Am J Physiol Heart Circ Physiol 292: H76-H82, 2007; Jaimes EA, Tian RX, Joshi M, Raij L. Am J Nephrol 29: 319-326, 2009). These studies were designed to test the hypothesis that nicotine worsens renal injury in db/db mice, a well-established model of diabetic nephropathy, and that reactive oxygen species play an important as mediators of these effects. For these studies, nicotine (100 mug/ml) was administered in the drinking water to control and db/db mice for 10 wk. Blood pressure was measured by the tail-cuff method, and urine was collected for proteinuria. At death, kidneys were collected for histology and molecular biology. The administration of nicotine did not result in significant changes in blood pressure or blood glucose and resulted in cotinine levels similar to those found in the plasma of smokers. In diabetic mice, the administration of nicotine significantly increased urinary protein excretion (1-fold), glomerular hypertrophy, and mesangial area ( approximately 20%). These changes were accompanied by significant increases in NADPH oxidase 4 ( approximately 30%) and increased nitrotyrosine and Akt expression. In vitro, we determined that nicotine has additive effects to high glucose on reactive oxygen species generation and Akt phosphorylation in human mesangial cells. These findings unveil novel mechanisms that may result in the development of novel strategies in the treatment and prevention of diabetic nephropathy in smokers.
详细资料
- 关键词: Animals; Blood Glucose/metabolism; Blood Pressure/physiology; Cells, Cultured; Diabetic Nephropathies/metabolism/pathology/*physiopathology; Disease Models, Animal; *Disease Progression; Humans; Kidney Glomerulus/metabolism/pathology/*physiopathology; Male; Mesangial Cells/metabolism/pathology; Mice; Mice, Inbred C57BL; NADPH Oxidase/metabolism; Nicotine/*pharmacology; Nicotinic Agonists/*pharmacology; Proto-Oncogene Proteins c-akt/metabolism; Reactive Oxygen Species/metabolism; Smoking/*adverse
- 文献种类: Journal Article
- 期刊名称: American Journal of Physiology. Renal Physiology
- 期刊缩写: Am J Physiol Renal Physiol
- 期卷页: 2010年第299卷第4期 F732-9页
- 地址: Division of Nephrology, University of Alabama at Birmingham, USA
- ISBN: 0363-6127
- 备注:PMID:20685820
学科领域生物医药 » 基础医学
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附件
Nicotine worsens the severity of nephropathy in diabetic mice: implications for the progression of kidney disease in smokers