Document Detail

Metabolism of arachidonic acid via the lipoxygenase pathway in human and murine glomeruli.
MedLine Citation:
PMID:  6403527     Owner:  NLM     Status:  MEDLINE    
Glomeruli isolated from murine and human renal cortex metabolize arachidonic acid to prostaglandins via the cyclooxygenase pathway but whether such glomeruli can also metabolize arachidonic acid via the lipoxygenase pathway is controversial. [1-14C]Arachidonic acid was incubated with glomeruli or glomerular fractions isolated from rat and human renal cortex. The products were extracted, purified by high performance liquid chromatography, and identified by comparison of their retention times with those of authentic hydroxyeicosatetraenoic acid (HETE) standards and by gas chromatography-mass spectrometry. At low substrate concentrations, human glomeruli synthesized in equivalent amounts 12- and 15-HETE, whereas rat glomeruli synthesized only 12-HETE and in larger quantities than in man. At higher substrate concentrations, both species synthesized 12- and 15-HETE and the rate of synthesis for both products was higher in human glomeruli. No other HETE was detected in either species. The lipoxygenase products were stored within the glomeruli and recovered almost equally in the 10,000 x g pellet and in the 100,000 X g supernatant of the homogenized glomeruli. The properties of the lipoxygenase system were the following: the enzyme was distributed equally in the membranes and the cytosol; 12-HETE accumulation was linear with time over 15 min; and 12-HETE production correlated linearly with the amount of glomerular protein. 12-Lipoxygenase activity was maximum at pH 7.5 (rat) or 9.0 (human) and at 40-42 degrees C (both species). Km values calculated at low concentrations of substrate (10-200 microM) were for 15-HETE, 125 and 667 microM with murine and human glomeruli, respectively, and for 12-HETE, 44 microM with the glomeruli of both species. This study demonstrates lipoxygenase activity in murine and, for the first time, in human glomeruli. The products of such enzymatic activity, 12- and 15-HETE, may mediate the glomerular inflammatory response in various experimental or spontaneous glomerular diseases.
J Sraer; M Rigaud; M Bens; H Rabinovitch; R Ardaillou
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  258     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1983 Apr 
Date Detail:
Created Date:  1983-05-05     Completed Date:  1983-05-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4325-30     Citation Subset:  IM    
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MeSH Terms
Arachidonic Acid
Arachidonic Acids / metabolism*
Chromatography, High Pressure Liquid
Kidney Cortex / enzymology*
Kidney Glomerulus / enzymology*
Lipoxygenase / metabolism*
Reg. No./Substance:
0/Arachidonic Acids; 506-32-1/Arachidonic Acid; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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