title: Differential disposition of lysophosphatidylcholine in diabetes compared with raised glucose: implications for prostaglandin production in the diabetic kidney glomerulus in vivo.
abstract: An early increased formation of renal prostaglandins in diabetes which follows the hydrolysis of cellular phospholipids by cytosolic phospholipase A2 is of considerable importance in determining subsequent cellular function. As the disposition of concomitantly formed lysophosphatidylcholine may also affect cellular function, we investigated the cellular fate of exogenous lysophosphatidylcholine in mesangial cell-enriched glomerular cores and showed that in cells taken from diabetic rats there is an increased net reformation of phosphatidylcholine. Positional distribution of labelled palmitate from sn-1 position palmitate-labelled lysophosphatidylcholine showed distribution to both sn-1 and sn-2 position of the phosphatidylcholine formed with a significantly increased sn-2 position labelling in diabetes. Although both a coenzyme A-dependent acyltransferase activity and a coenzyme A-independent transacylase activity could be shown in these cells, the increased phosphatidylcholine formation in cells taken from diabetic animals was due to an increase in coenzyme A-independent transacylase activity. By contrast, an increase in coenzyme-A independent transacylase activity could not be demonstrated in cultured mesangial cells maintained with prolonged raised glucose concentrations. Cell homogenates possess the ability to transfer fatty acid from lysophosphatidylcholine to lysophosphatidylcholine and lysophosphatidylethanolamine with subsequent formation of phosphatidylcholine and phosphatidylethanolamine, respectively. In preparations from diabetic animals phosphatidylethanolamine formed in this manner was increased in the presence of an inhibitor of cytosolic phospholipase A2, indicating that it may provide a substrate for phospholipase A2 activity; an effect not seen in cultured cells maintained at raised glucose concentrations. It is concluded that one effect of an altered disposition of lysophosphatidylcholine in cells from diabetic animals would be to spare fatty acids released following phospholipase A2 hydrolysis of phospholipid, possibly providing the substrate for prostaglandin production, an effect not seen with raised glucose alone.
authors.affiliation: University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia.
authors.forename: M E
authors.initials: ME
authors.lastname: Dunlop
authors.forename: E
authors.initials: E
authors.lastname: Muggli
authors.forename: S
authors.initials: S
authors.lastname: Clark
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000378:metabolism* / Q000494:pharmacology; D008245:Lysophospholipase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008244:Lysophosphatidylcholines; D011453:Prostaglandins; D000217:Acyltransferases; D008245:Lysophospholipase; D005947:Glucose