Cardiomyocyte-specific disruption of Serca2 in adult mice causes sarco(endo)plasmic reticulum stress and apoptosis.

Reduced sarco(endo)plasmic reticulum (SR) Ca(2+) ATPase (SERCA2) contributes to the impaired cardiomyocyte Ca(2+) homeostasis observed in heart failure. We hypothesized that a reduction in SERCA2 also elicits myocardial ER/SR stress responses, including unfolded protein responses (UPR) and cardiomyocyte apoptosis, which may additionally contribute to the pathophysiology of this condition. Left ventricular myocardium from mice with cardiomyocyte-specific tamoxifen-inducible disruption of Serca2 (SERCA2 KO) was compared with aged-matched controls.

Effects of bilirubin ditaurate overload on canalicular membrane function and ultrastructure of the pig liver.

Aim: Bilirubin overload caused by haemolysis of transfused blood and breakdown of extravasated blood constitutes an important causative factor of jaundice in trauma patients. Intravenous infusions of large amounts of unconjugated bilirubin (UCB) block biliary phospholipid secretion and produce canalicular membrane lesions in pigs, putatively because of enhanced cytotoxicity of bile. Severe intrahepatic cholestasis is the functional end result.

ABCB4 sequence variations in young adults with cholesterol gallstone disease.

Background And Aims: Mutations in the gene encoding the ABCB4 [adenosine triphosphate (ATP)-binding cassette, sub-family B (MDR/TAP), member 4] transporter lower phosphatidylcholine output into bile and contribute to cholesterol gallstone formation by decreasing the solubility of cholesterol in bile. Mutations in ABCB4 have been identified in patients with low phospholipid-associated cholelithiasis. The aim of the present study was to determine the types and frequencies of ABCB4 mutations in cholecystectomized patients aged <40 years.

Gene expression profiles reflect sclerosing cholangitis activity in abcb4 (-/-) mice.

Objective: Abcb4 (-/-) mice secrete phosphatidylcholine-deficient bile and develop sclerosing cholangitis (SC), a condition that involves differential hepatic transcription of genes governing inflammation, tissue remodelling and fibrosis. The objective of this study was to test the hypothesis that genes involved in the regulation of tissue inflammation and fibrosis display transcription rates that parallel differences in abcb4 (-/-) SC activity. The activity of abcb4 (-/-) SC can be altered through dietary intervention: abcb4 (-/-) mice fed cholic acid (CA) display high SC activity, whereas ursodeoxycholic acid (UDCA)-fed mice display low SC activity.

Multiple inflammatory-, tissue remodelling- and fibrosis genes are differentially transcribed in the livers of Abcb4 (-/ - ) mice harbouring chronic cholangitis.

Objective: Abcb4 (-/-) mice secrete phosphatidylcholine-free, cytotoxic bile and develop chronic cholangitis. The aim of this study was to identify differentially transcribed genes whose products contribute to the liver tissue pathology during this disease.

Material And Methods: Hepatic gene transcription was measured in 3-, 6-, 9- and 20-week-old Abcb4 (-/-) mice (FVB.

Differential regulation of vacuolar H+ -ATPase and Na+/H+ exchanger 3 in rat cholangiocytes after bile duct ligation.

The cholangiocytes lining the intrahepatic bile ducts modify the primary secretion from the hepatocytes. The cholangiocytes secrete HCO (3)(-) into bile when stimulated with secretin in many species, including man. However, in rats, secretin stimulation neither affects biliary HCO (3)(-) concentration nor bile flow, whereas following bile duct ligation (BDL) it induces hypercholeresis with significant increase of NaHCO(3) concentration.