[The mechanism of action of E.coli endotoxin on oxidative phosphorylation of the rat liver mitochondria].
The effects of E.coli endotoxin on oxidative phosphorylation were investigated in vitro using isolated rat liver mitochondria. The respiratory control index (RCI) was significantly decreased by preincubation of mitochondria for 20 min. at 30 degrees C in the presence of the endotoxin, which repressed dose-dependently the state 3 respiration. The extent of the repression of this state 3 respiration was comparable with that of the exchange reaction of adenine nucleotide. The endotoxin, however, did not inhibit several mitochondrial enzymes including the electron transport system at the enzyme level. The exchange reaction and the number of the ADP-binding sites of the adenine nucleotide carrier were assayed using [14C] ADP and [3H] carboxyatractyloside, respectively. The exchange reaction was repressed by 72% and the number of binding site of carboxyatractyloside was decreased by 20% by the endotoxin (100 micrograms/mg mitochondrial protein). These effects of endotoxin on the adenine nucleotide carrier were additionally enhanced by the Ca2+ ion. The occurrence of these effects was prevented by EGTA or dibucaine, a potent inhibitor of phospholipase A2. These results suggested that the endotoxin may activate phospholipase A2 which may harm the lipid layer of the mitochondrial membrane.
D000818:Animals; D003864:Depression, Chemical; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D066298:In Vitro Techniques; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains
D004731:Endotoxins; D000226:Mitochondrial ADP, ATP Translocases; D010741:Phospholipases A; D054467:Phospholipases A2