Fibrinogen-y proteolysis and solubility dynamics during apoptotic @entity19 XXXX : heparin prevents and treats liver damage.

@entity66 @entity548 @entity19 @entity5642 @entity9699 @entity1443 @entity99 @entity493
@entity9699 ( @entity9699 )-mediated hepatocyte apoptosis occurs in the context of @entity99 that can be accompanied by @entity5642 ( @entity5642 ). We tested the hypothesis that analysis of selected protein fractions from livers undergoing apoptosis will shed light on mechanisms that are involved in @entity99 that might be amenable to intervention. Proteomic analysis of the major insoluble liver proteins after @entity9699 exposure for 4-5 hours identified fibrinogen-y (FIB-y) dimers and FIB-y-containing high molecular mass complexes among the major insoluble proteins visible via Coomassie blue staining. Presence of the FIB-y-containing products was confirmed using FIB-y-specific antibodies. The FIB-y-containing products partition selectively and quantitatively into the liver parenchyma after inducing apoptosis. Similar formation of FIB-y products occurs after @entity1443 administration. The observed intrahepatic @entity5642 raised the possibility that heparin therapy may ameliorate @entity9699 -mediated @entity99 . Notably, heparin administration in @entity19 4 hours before or up to 2 hours after @entity9699 injection resulted in a @entity99 -including @entity548 , serum @entity493 aminotransferase, caspase activation, and liver apoptosis-compared with heparin-untreated @entity19 . Heparin did not directly interfere with @entity9699 -induced apoptosis in isolated hepatocytes, and heparin-treated @entity19 survived the @entity9699 -induced @entity99 longer compared with heparin-untreated animals. There was a sharp, near-simultaneous rise in @entity9699 -induced @entity66 , with @entity5642 remaining stable while apoptosis continued to increase. CONCLUSION: Formation of FIB-y dimers and their high molecular mass products are readily detectable within the liver during @entity19 apoptotic @entity99 . Heparin provides a potential therapeutic modality, because it not only prevents extensive @entity9699 -related @entity99 but also limits the extent of injury if given at early stages of injury exposure.
