| Nicotine worsens the severity of nephropathy in diabetic mice: implications for the progression of kidney disease in smokers. | |
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MedLine Citation:
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PMID: 20685820 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 μg/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 (∼20%). These changes were accompanied by significant increases in NADPH oxidase 4 (∼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. |
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Authors:
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Ping Hua; Wenguang Feng; Shaonin Ji; Leopoldo Raij; Edgar A Jaimes |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-08-04 |
Journal Detail:
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Title: American journal of physiology. Renal physiology Volume: 299 ISSN: 1522-1466 ISO Abbreviation: Am. J. Physiol. Renal Physiol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-04 Completed Date: 2010-10-26 Revised Date: 2011-04-28 |
Medline Journal Info:
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Nlm Unique ID: 100901990 Medline TA: Am J Physiol Renal Physiol Country: United States |
Other Details:
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Languages: eng Pagination: F732-9 Citation Subset: IM |
Affiliation:
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Division of Nephrology, University of Alabama at Birmingham, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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 effects* Tyrosine / analogs & derivatives, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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ES014948/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Nicotinic Agonists; 0/Reactive Oxygen Species; 3604-79-3/3-nitrotyrosine; 54-11-5/Nicotine; 55520-40-6/Tyrosine; EC 1.6.-/Nox4 protein, mouse; EC 1.6.3.1/NADPH Oxidase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
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