Impairments in hepatocyte phosphoinositide metabolism in endotoxemia.
The status of phospholipid metabolism and inositol lipids-mediated transmembrane signaling in rat hepatocytes was analyzed during chronic, nonlethal endotoxemia. Rats were infused intravenously (IV) with Escherichia coli endotoxin (ET) via subcutaneously implanted osmotic pumps at a rate of 0.1 mg/100 g bw/day. The experiments were performed after 30 hours of ET or sterile saline (NaCl) infusion, in hepatocytes prelabelled "in vitro" with 32P (15 microCi/mL) and further stimulated with vasopressin (VP, 0.23 mumol/L). Similar experiments were done with food-restricted animals, whose food intake was matched with the voluntary intake of ET-infused rats. Uptake of 32P label into phosphatidic acid (PA), phosphatidylinositol 4-phosphate (PIP), and phosphatidylinositol 4,5-bisphosphate (PIP2) occurs rapidly in cells from pair-fed, saline and ET-infused animals, and reaches a plateau between 60 and 80 minutes of incubation. Labeling of phosphatidylinositol (PI), phosphatidylethanolamine (PE), and phosphatidylcholine (PC) proceeds linearly after a ten-minute lag period for PI and 20 minutes for the two other lipids. The nutritional state greatly affects the distribution of 32P uptake into lipids, resulting in very low labeling of PA and PI and a high labeling of poly-PI as compared with control (taken from untreated rats) cells. In ET-v saline-infused rats, the labeling of PI and PE was depressed concomitantly with a proportional increase in the labeling of PIP and PC. The ability of VP to induce polyphosphoinositide (poly-PI) degradation in hepatocytes from saline-infused animals was similar to that observed in control cells.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D004731:Endotoxins / Q000097:blood / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010712:Phosphatidic Acids / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014667:Vasopressins / Q000494:pharmacology
D004731:Endotoxins; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D010743:Phospholipids; D014667:Vasopressins