Dietary manipulation of delta-6-desaturase modifies phospholipid arachidonic acid levels and the urinary excretion of calcium and oxalate in the rat: insight in calcium lithogenesis.
An anomalous n-6 polyunsaturated fatty acid composition in plasma and erythrocyte membrane phospholipids, namely increased levels of arachidonic acid (AA), has been reported in calcium nephrolithiasis and has been proposed to play an important role in its pathogenesis. To confirm this, in rats we modified phospholipid AA levels by dietary manipulation of the delta-6-desaturase, the rate-limiting enzyme of the fatty acid biosynthetic pathway, and evaluated the effect on cellular and renal functions predisposing to lithogenesis. Increased AA levels led to conditions at risk for nephrolithiasis: higher oxalate flux and lower sodium cotransport in erythrocytes and a rise in urinary prostaglandin E2, calcium, sodium, and oxalate levels; reduced AA levels reversed these changes. In vitro, in human erythrocytes the incorporation of exogenous AA into membranes increased band 3 protein phosphorylation directly activating the Ser/Thr protein kinase CK1 and induced a parallel raise in band 3-mediated oxalate transport. These findings demonstrate the pivotal role of phospholipid AA in modulating erythrocyte and renal transport of calcium and oxalate.
Gambaro
G
G
Department of Medical and Surgical Sciences, School of Medicine, University of Padova, Italy.
Bordoni
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A
Hrelia
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S
Bordin
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L
Biagi
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P
Semplicini
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A
Clari
G
G
Manzato
E
E
Baggio
B
B
D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D016718:Arachidonic Acid / Q000097:blood* / Q000494:pharmacology; D002118:Calcium / Q000652:urine*; D047390:Casein Kinase II; D047388:Casein Kinases; D004032:Diet; D015232:Dinoprostone / Q000652:urine; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000201:enzymology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D006801:Humans; D050602:Linoleoyl-CoA Desaturase; D008099:Liver / Q000201:enzymology; D008297:Male; D009397:Nephrocalcinosis / Q000209:etiology / Q000378:metabolism*; D010070:Oxalates / Q000652:urine*; D010743:Phospholipids / Q000097:blood*; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine
D001457:Anion Exchange Protein 1, Erythrocyte; D010070:Oxalates; D010743:Phospholipids; D016718:Arachidonic Acid; D012964:Sodium; D044943:Fatty Acid Desaturases; D050602:Linoleoyl-CoA Desaturase; D011494:Protein Kinases; D047390:Casein Kinase II; D047388:Casein Kinases; D017346:Protein Serine-Threonine Kinases; D015232:Dinoprostone; D002118:Calcium