Document Detail


Differential nephron HO-1 expression following glomerular epithelial cell injury.
MedLine Citation:
PMID:  16601358     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: In proteinuria of glomerular origin there is upregulation of heme-oxygenase (HO), the rate-limiting enzyme of heme degradation, in the nephron in a segment-specific manner. To better characterize this phenomenon, we employed a model of proteinuria resulting from disruption of the glomerular capillary permeability barrier to protein by administration of the glomerular epithelial cell toxin puromycin aminonucleoside (PAN) to rats. In this model, we assessed nephron distribution of the expression of the inducible HO isoform, HO-1, and the role of free radicals in modulating HO-1 expression. METHODS: Rats were injected with either vehicle (dimethyl sulfoxide) or PAN or the spin trap free radical stabilizer alpha-phenyl-N-tert butyl nitrone (PBN), or with both PAN and PBN. Ten days following the PAN injection, urine protein, creatinine, nitric oxide (NO) and malonyldialdehyde (MDA) were measured. Kidney sections and protein lysates were assessed for changes in HO-1 expression by immunohistochemistry and Western blot analysis. RESULTS: In control animals (DMSO or PBN alone) there was no proteinuria and very weak or absent HO-1 staining in nephron segments. PAN treatment induced proteinuria and increased urine MDA excretion. In these animals, there was a robust HO-1 expression mainly in tubules and in glomerular parietal but not visceral epithelial cells. Unilateral ureteral obstruction to interrupt glomerular filtration in animals treated with PAN abrogated tubular HO-1 expression in the kidney ipsilateral to the obstruction. Administration of PBN to PAN-treated animals reduced proteinuria and MDA excretion while it markedly augmented tubular HO-1 expression. This augmentation was prominent in tubular cells of the inner cortex/outer medulla. CONCLUSIONS: These observations indicate that upregulation of nephron HO-1 following disruption of the glomerular permeability barrier occurs at sites downstream of this barrier and is mediated by a filtered HO-1 inducer(s). Scavenging of free radicals potentiates the effect of this inducer and unmasks nephron segments most and least capable of upregulating HO-1.
Authors:
Prasun K Datta; Sreenivas Reddy; Mukut Sharma; Elias A Lianos
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-04-05
Journal Detail:
Title:  Nephron. Experimental nephrology     Volume:  103     ISSN:  1660-2129     ISO Abbreviation:  Nephron Exp. Nephrol.     Publication Date:  2006  
Date Detail:
Created Date:  2006-07-19     Completed Date:  2006-08-02     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  101159770     Medline TA:  Nephron Exp Nephrol     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  e131-8     Citation Subset:  IM    
Copyright Information:
Copyright 2006 S. Karger AG, Basel
Affiliation:
Laboratory of AIDS Pathogenesis and Molecular Therapeutics, Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, PA 19122, USA. dattapk@temple.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Cyclic N-Oxides
Disease Models, Animal
Free Radical Scavengers
Heme Oxygenase-1 / metabolism*
Kidney Glomerulus / metabolism*,  pathology
Male
Nephrons / metabolism*,  pathology
Nitrogen Oxides
Permeability
Proteinuria / physiopathology*
Puromycin Aminonucleoside
Rats
Rats, Sprague-Dawley
Up-Regulation
Grant Support
ID/Acronym/Agency:
DK51357/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Cyclic N-Oxides; 0/Free Radical Scavengers; 0/Nitrogen Oxides; 3376-24-7/phenyl-N-tert-butylnitrone; 58-60-6/Puromycin Aminonucleoside; EC 1.14.99.3/Heme Oxygenase-1

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