The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Bid antisense attenuates bile acid-induced apoptosis and cholestatic liver injury.

Bile acids cause liver injury during cholestasis by inducing hepatocyte apoptosis by both Fas-dependent and -independent mechanisms. However, the Fas-independent apoptosis also appears to be death receptor-mediated. Because death receptor-mediated apoptosis in hepatocytes requires proapoptotic Bcl-2 BH3 domain only protein Bid, we postulated that Fas-independent but death receptor- mediated bile acid cytotoxicity would be Bid-dependent. We used Fas-deficient lymphoproliferative (lpr) mouse hepatocytes for these studies, and inhibited Bid expression using an antisense approach. Glychochenodeoxycholate (GCDC) was used to induce apoptosis. Bid cleavage and translocation to mitochondria was observed in GCDC-treated cells as assessed by immunoblot analysis and confocal imaging of Bid-green fluorescent protein, respectively. Bid translocation to mitochondria was associated with cytochrome c release. A Bid antisense 2'-MOE modified oligonucleotide inhibited Bid expression in hepatocytes and markedly attenuated hepatocytes apoptosis by GCDC. Treatment of lpr mice with Bid antisense also ameliorated liver injury following bile duct ligation of the mice, a model of extrahepatic cholestasis. These results suggest that bile acid cytotoxicity is Bid-dependent despite the absence of Fas. Bid antisense therapy is a promising approach for the treatment of cholestatic liver injury.[1]

References

  1. Bid antisense attenuates bile acid-induced apoptosis and cholestatic liver injury. Higuchi, H., Miyoshi, H., Bronk, S.F., Zhang, H., Dean, N., Gores, G.J. J. Pharmacol. Exp. Ther. (2001) [Pubmed]
 
WikiGenes - Universities