Prevention of thromboxane B2-induced hepatocyte plasma membrane bleb formation by certain prostaglandins and a proteinase inhibitor.
Isolated hepatocytes incubated in the presence of thromboxane B2 developed many plasma membrane blebs which are a characteristic feature of toxic or ischaemic cell injury. When hepatocytes were incubated in the presence of both thromboxane B2 and the non-lysosomal proteinase inhibitor, leupeptin, were also well protected from the formation of blebs. This implies that thromboxane B2 is able to activate non-lysosomal proteinases which appear to attack certain cytoskeletal proteins. The data presented are consistent with thromboxane B2 acting as an intermediary in a proposed mechanism of cell injury and death in which elevated cytosolic free Ca2+ levels activate phospholipase A2 and the arachidonic acid cascade.
Horton
A A
AA
School of Biochemistry, University of Birmingham, U.K.
Wood
J M
JM
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects* / Q000648:ultrastructure; D011464:Epoprostenol / Q000494:pharmacology*; D007976:Leupeptins / Q000494:pharmacology*; D008099:Liver / Q000648:ultrastructure*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D013929:Thromboxane B2 / Q000494:pharmacology*
D007976:Leupeptins; D009842:Oligopeptides; D011459:Prostaglandins E, Synthetic; D000001:Calcimycin; D013929:Thromboxane B2; D011464:Epoprostenol; C032854:leupeptin; D015064:16,16-Dimethylprostaglandin E2; D002118:Calcium