Cadmium ion-induced alterations of phospholipid metabolism in endothelial cells.
Cadmium exposure is capable of causing acute and chronic lung injuries, but the specific pathogenetic mechanisms are uncertain. The effects of cadmium ion (Cd2+) on phospholipid metabolism were examined in cultured bovine pulmonary artery endothelial cells (BPAEC), as endothelial cells appear to be particularly vulnerable to the toxic effects of this metallic ion. Exposure of radiolabeled BPAEC to millimolar concentrations of Cd2+ causes liberation of substantial amounts of [3H]arachidonic acid ([3H]AA), but only small amounts of [14C]stearic acid, from each of the major phospholipid subclasses. Analyses of hydrolytic products in BPAEC radiolabeled with [3H]myo-inositol and exposed to Cd2+ indicate that degradation of complex phospholipids is mediated by phospholipase A2. The ability of BPAEC to incorporate fatty acids or lysophosphatides into complex phospholipids is similarly impaired after exposure to Cd2+, suggesting that the liberation of [3H]AA might be due to impairment of reacylation mechanisms and not to increased hydrolytic activity of phospholipase A2. Of the two enzymes involved in reacylation reactions, Cd2+ is found to inhibit the activity of arachidonyl-specific acyl coenzyme A synthetase but not the activity of acyltransferase. Cd2+ also causes a profound time- and dose-dependent depletion of adenosine triphosphate levels in BPAEC, and these changes closely correlate with the liberation of [3H]AA. We suggest that impairment of reacylation mechanisms, and the consequent accumulation of arachidonic acid, may be important in the development of the acute inflammatory reaction that is characteristic of Cd(2+)-induced lung injury.
Nelson
J M
JM
Pulmonary Section-111N, Veterans Administration Medical Center, Minneapolis, MN 55417.
Duane
P G
PG
Rice
K L
KL
Niewoehner
D E
DE
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002104:Cadmium / Q000633:toxicity*; D002413:Cations, Divalent; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism*; D013229:Stearic Acids / Q000378:metabolism
D002413:Cations, Divalent; D005230:Fatty Acids, Nonesterified; D008244:Lysophosphatidylcholines; D010743:Phospholipids; D013229:Stearic Acids; D002104:Cadmium; D016718:Arachidonic Acid; C031183:stearic acid; D007294:Inositol; D000255:Adenosine Triphosphate; D010741:Phospholipases A; D054467:Phospholipases A2