Yasutoshi Muto

Impaired synthesis of retinol-binding protein and transthyretin in rat liver with bile duct obstruction

To gain further insight into the protein metabolism in bile duct-obstruction, we examined the synthesis of retinol-binding protein (RBP) and transthyretin (TTR) in rats with common bile duct-ligation. In these rats, liver and plasma levels of RBP and TTR decreased markedly, whereas liver retinoid contents remained unchanged. Although there appeared no decrease in the total amount of RBP or TTR mRNA expressed in the liver, the subcellular distribution of these mRNAs changed from the membrane-bound polysome fraction to the membrane-unbound polysome fraction. This abnormal distribution recovered rapidly after biliary drainage, resulting in the subsequent recovery of the plasma RBP and TTR levels. These observations suggest that cholestasis inhibits the synthesis and secretion of RBP and TTR by disrupting the binding of their mRNAs to membrane-bound polysomes. Plasma levels of RBP and TTR might be sensitive indicators of the recovery of protein synthesis after biliary drainage in patients with obstructive biliary disorders.

Reduced intestinal apo A-IV mRNA levels in patients with liver cirrhosis

Although fat malabsorption is often observed in patients with liver cirrhosis, it is unknown whether intestinal apo A-IV is related to the malabsorption in these patients. We measured serum apo A-IV concentrations and intestinal apo A-IV mRNA levels in seven patients and seven sex- and age-matched control subjects. The biopsy was performed on the second portion of the duodenum through endoscopy in all subjects at overnight fast. Total RNA was isolated from biopsy specimens and apo A-IV mRNA levels were determined by slot blot analysis. Although there was no difference in serum apo A-IV concentrations between the two groups (liver cirrhosis; 9.1 ± 3.2 mg/dl, control; 8.5 ± 2.8 mg/dl), apo A-IV mRNA levels in the patients were significantly decreased (5.07 ± 1.26 RAU, P < 0.05) compared with those of control subjects (7.13 ± 1.90 RAU). The constant serum apo A-IV level despite low mRNA abundance possibly indicates the increased translational rate or the delayed clearance of apo A-IV in cirrhosis.

Developemental Induction of Hepatic Glucokinase in Growing Rats

発達過程における白ネズミ肝GKならびに小腸二糖類分解酵素活性を経時的に測定し, さらにホルモン投与の影響を検討した。1) 肝GK活性は出生後16日目までは検出されないが, 離乳期の25日目を境として急激に上昇し30日目でほぼ成熟白ネズミのレベルに近づく。一方, HK活性はこの期間中なんらの変動も示さなかった。2) Estradiol投与は性臓器の重量に著しい影響を及ぼしたが, 肝GK活性に対しては必ずしも抑制効果を示さなかった。3) Hydrocortisoneはブドウ糖の同時投与によって生後22日目の肝GK活性を有意に増加させたが, 生後30日目では著明な効果を示さなかった。Tst, Prg, GlgならびにGH投与は肝GK活性に対し著明な影響を示さなかった。4) 小腸maltaseならびにsucrase活性はそれぞれ生後15日および18日より上昇傾向を示し, 22日および26日で最大のレベルに達した。これらは明らかに肝GK誘導に先行していた。