Defect in an intrahepatic degradation of apolipoprotein B in suncus: an animal model of hypobetalipoproteinemia.
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.
Liang
Y Q
YQ
Department of internal Medicine, Teikyo University School of Medicine, Tokyo.
Kinoshita
M
M
Muto
T
T
Fujimaki
Y
Y
Matsuki
N
N
Saito
H
H
Yamanaka
M
M
Teramoto
T
T
D000818:Animals; D001055:Apolipoproteins B / Q000096:biosynthesis / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006995:Hypobetalipoproteinemias / Q000378:metabolism*; D007976:Leupeptins / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D012788:Shrews
D001055:Apolipoproteins B; D007976:Leupeptins; C063261:acetylleucyl-leucyl-norleucinal