Modulation of Fas-FasL related apoptosis by PBN in the early phases of choline deficient diet-mediated hepatocarcinogenesis in rats.
This study focused on the detection of apoptosis related events in very early phases of choline-deficient (CD)-induced hepatocarcinogenesis (at 2-5 weeks). Flow cytometry of isolated intact primary hepatocytes from CD diet fed rats indicated increased expression of the apoptosis-associated protein Fas. Increased apoptosis in CD-treated livers was confirmed by Western blot analyses of caspases and cytochrome c. This study was also able to detect differences in apoptotic events following phenyl butyl nitrone (PBN) treatment. Fas expression was inhibited by PBN, indicating that PBN is anti-apoptotic. It is speculated that in the early stages of CD-induced hepatotoxicity, PBN is involved in inhibiting pro-inflammatory factor-driven apoptosis of normal hepatocytes, which protects against the initiation of carcinogenesis. The CD diet model is also considered as a model for non-alcoholic steatohepatitis (NASH) in humans and early expression of Fas could also be a good index of the progression of NASH.
Inoue
Yoshiko
Y
Free Radical Biology and Aging Research Program, Oklahoma City, OK 73104, USA.
Asanuma
Taketoshi
T
Smith
Nataliya
N
Saunders
Debra
D
Oblander
Jenny
J
Kotake
Yashige
Y
Floyd
Robert A
RA
Towner
Rheal A
RA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D002794:Choline / Q000008:administration & dosage; D002796:Choline Deficiency / Q000150:complications*; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004032:Diet; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D019014:fas Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism
D003497:Cyclic N-Oxides; C491898:Fas protein, rat; D016166:Free Radical Scavengers; D019014:fas Receptor; C029217:phenyl-N-tert-butylnitrone; D002794:Choline