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J. Biochem, 1998, Vol. 123, No. 1 28-32
© 1998 Japanese Biochemical Society

research-article

Defect in an Intrahepatic Degradation of Apolipoprotein B in Suncus: An Animal Model of Hypobetalipoproteinemia1

Yi-qiang Liang*, Makoto Kinoshita*, Tomomi Muto*, Yuko Fujimaki*, Norio Matsuki*, Hiroshi Saito{dagger}, Masami Yamanaka* and Tamio Teramoto*,2

*Department of internal Medicine, Teikyo University School of Medicine 11-1 Kaga 2-chome, Itabashi-ku, Tokyo 173
{dagger}Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo Bunkyo-ku, Tokyo 113

2To whom correspondence should be addressed. Tel: +81-3-3964-1211 (Ext. 1542), Fax: +81-3-3964-7637, E-mail: QZG10707{at}niftyserve.or.jp

We have previously shown that fatty liver is easily induced in suncus by starvation and that the plasma level of apolipoprotein B (apo B) is very low. We also found that hepatic acyl coenzyme A cholesterol acyltransferase (ACAT) activity is almost absent in the animals, resulting in decreased cholesteryl ester contents in the liver. A deficiency of cholesteryl ester in suncus liver may be one of the reasons for the defect in the assembly process of apo B-containing lipoproteins, leading to a low level of plasma apo B. Another possible explanation for the induction of fatty liver in suncus is a defect in apo B-processing in the liver. In this study, we investigated the hepatic synthetic rate and intrahepatic degradation of apo B using primary cultured hepatocytes derived from suncus and rats. In order to estimate intrahepatic degradation of apo B, we added N-acetylleucyl-leucynorleucinal to the culture medium as an inhibitor of apo B degradation. The basal synthesis of apo B in suncus hepatocytes was 50% of that in rat. Intracellular degradation of apo B was not observed in suncus hepatocytes, while it was obvious in rat hepatocytes. This evidence suggests that the lower secretion rate of apo B-lipoprotein is not due to the intrahepatic degradation of apo B, but may be due to the low synthetic rate of apo B.

1This study was supported in part by Grant-in-Aid for Scientific Research (No. 08671182, 07557311) from the Ministry of Education, Science, Sports and Culture of Japan and grants from Sasakawa health science foundation, and Japan-China medical association.


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