16-16-dimethylprostaglandin-e2 and leupeptin

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.

Topics: 16,16-Dimethylprostaglandin E2; Animals; Calcimycin; Calcium; Cell Membrane; Epoprostenol; Leupeptins; Liver; Male; Oligopeptides; Prostaglandins E, Synthetic; Rats; Thromboxane B2