Etiologic significance of defects in cholesterol, phospholipid, and bile acid metabolism in the liver of patients with intrahepatic calculi
| Autor: | Koji Oda, Junichi Kamiya, Yuichi Sugiyama, Junichi Shoda, Hiroshi Miyazaki, Li Feng, Masahito Kano, Yasushi Matsuzaki, David E. Cohen, Yuji Nimura, Kosei Ito, Naomi Tanaka, Hiroshi Suzuki |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Male medicine.medical_specialty medicine.drug_class Phospholipid Phosphatidylethanolamine Binding Protein Gallbladder Stone Biology Androgen-Binding Protein Calculi Bile Acids and Salts Pathogenesis chemistry.chemical_compound Cholestasis Internal medicine medicine Bile Humans Tissue Distribution RNA Messenger Phospholipid Transfer Proteins Cholesterol 7-alpha-Hydroxylase Phospholipids Aged Membranes Hepatology Bile acid Cholesterol Liver Diseases Bile Canaliculi Phosphatidylcholine transfer protein Intracellular Membranes Middle Aged Lipid Metabolism medicine.disease Endocrinology Liver chemistry Microsomes Liver Female Hydroxymethylglutaryl CoA Reductases Carrier Proteins |
| Zdroj: | Hepatology. 33:1194-1205 |
| ISSN: | 0270-9139 |
| DOI: | 10.1053/jhep.2001.23936 |
| Popis: | Intrahepatic calculi, highly prevalent in the Far East, including Japan, are characterized clinically by chronic proliferative cholangitis with frequent stone recurrences. Intrahepatic calculi consist of 2 groups, i.e., brown pigment stones, including a high cholesterol content, and cholesterol stones, with the former predominating. To gain insights into the pathogenesis of intrahepatic calculi, cholesterol and bile acid biosynthesis, as well as alterations in intracellular transport and/or canalicular secretion of phospholipid and bile acid were investigated in liver of patients with intrahepatic calculi. Enzyme activities of 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase were increased (12.8 ± 1.9 pmol/min/mg protein, mean ± SEM vs. 5.5 ± 0.4 in controls; P < .01) and cholesterol 7 α-hydroxylase activities were decreased (1.3 ± 0.4 vs. 4.9 ± 0.6; P < .01) in liver specimens of patients with brown pigment stones. In addition, messenger RNA (mRNA) levels of multidrug resistance P-glycoprotein 3 (MDR3 Pgp) and phosphatidylcholine transfer protein (PCTP) were markedly low in the liver specimens compared with the levels in specimens of control subjects, gallbladder stone patients, and patients with obstructive cholestasis. The protein levels and the immunohistochemical staining were decreased for MDR3 Pgp and PCTP in the liver. Consistently, the concentrations of phospholipid were markedly reduced in the hepatic bile from both affected and unaffected hepatic segments. In patients with intrahepatic calculi, biliary cholesterol supersaturation and the formation of cholesterol-rich brown pigment as well as cholesterol stones may be attributed to decreased hepatic transport and biliary secretion of phospholipids, in the setting of increased cholesterogenesis and decreased bile acid synthesis. (HEPATOLOGY 2001;33:1194-1205.) |
| Databáze: | OpenAIRE |
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