AJP - GI Watch the video to see how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol 290: G1339-G1346, 2006. First published February 16, 2006; doi:10.1152/ajpgi.00509.2005
0193-1857/06 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
290/6/G1339    most recent
00509.2005v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (20)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Feldstein, A. E.
Right arrow Articles by Gores, G. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Feldstein, A. E.
Right arrow Articles by Gores, G. J.

LIVER AND BILIARY TRACT

Bax inhibition protects against free fatty acid-induced lysosomal permeabilization

Ariel E. Feldstein,1 Nathan W. Werneburg,2 ZhengZheng Li,1 Steven F. Bronk,2 and Gregory J. Gores2

1Department of Pediatric Gastroenterology and Cell Biology, Cleveland Clinic Foundation, Cleveland, Ohio; and 2Mayo Clinic College of Medicine, Rochester, Minnesota

Submitted 27 October 2005 ; accepted in final form 24 January 2006

Lysosomal permeabilization is a key feature of hepatocyte lipotoxicity, yet the mechanisms mediating this critical cellular event are unclear. This study examined the mechanisms involved in free fatty acid (FFA)-induced lysosomal permeabilization and the role of Bax, a Bcl-2 family member, in this event. Exposure of liver cells to palmitate induced Bax activation and translocation to lysosomes. Studies to suppress Bax activation either by pharmacological approaches or small interfering-RNA-mediated inhibition of Bax expression showed that lysosomal permeabilization is Bax dependent. In addition, palmitate treatment resulted in a significant decrease in Bcl-XL, a Bax antagonist. Moreover, forced Bcl-XL expression blocked lysosomal permeabilization. Lysosomal permeabilization by FFA was ceramide and caspase independent. Finally, paradigms that inhibit lysosomal permeabilization also reduced apoptosis. In conclusion, these data strongly support a regulatory role for Bax in FFA-mediated lysosomal permeabilization and subsequent cell death.

nonalcoholic fatty liver disease; lysosomes; Bax; Bcl-2 family; cathepsin B


Address for reprint requests and other correspondence: G. J. Gores, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905 (e-mail: gores.gregory{at}mayo.edu)




This article has been cited by other articles:


Home page
 Pharmacol. Rev.Home page
N. Anderson and J. Borlak
Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis
Pharmacol. Rev., September 1, 2008; 60(3): 311 - 357.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2006 by the American Physiological Society.