Chronic hepatitis in interferon-gamma transgenic mice is associated with elevated CPP32-like activity and interleukin-1beta-converting enzyme activity suppression.
Interferon-gamma (IFN-gamma) transgenic mice strongly express IFN-gamma in the liver and develop chronic hepatitis. Furthermore, hepatocyte apoptosis was shown by the TdT-mediated dUTP-biotin nick endlabeling method. In the present study, interleukin-1beta-converting enzyme (ICE) and CPP32-like protease activities in the liver of IFN-gamma transgenic mice were measured, using the synthetic substrates Ac-YVAD-MCA and Ac-DEVD-MCA. Plasma aspartate aminotransferase and alanine aminotransferase activities as well as CPP32-like activity were significantly elevated, while ICE activity was significantly reduced. The addition of the ICE inhibitor Ac-YVAD-CHO to IFN-gamma transgenic mouse liver cell cytosol had no effect on the CPP32 activity, in contrast to a CPP32 inhibitor. The present results indicate that chronic hepatitis in the IFN-gamma transgenic mouse is associated with a decrease in ICE and induction of CPP32-like activity.
Okamoto
T
T
Research Laboratories, Nippon Chemiphar Co., Ltd., Saitama, Japan.
Nakano
Y
Y
Yamakawa
T
T
Hara
K
K
Yamamura
K I
KI
Hino
O
O
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006520:Hepatitis, Animal / Q000201:enzymology* / Q000235:genetics; D006521:Hepatitis, Chronic / Q000201:enzymology* / Q000235:genetics; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1