Related Experiment Video
Updated: Jul 16, 2026
08:56
Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
Familial intrahepatic cholestasis 1: studies of localization and function
1Department of Physiology, Tufts University School of Medicine, Boston, MA 02111, USA.
Hepatology (Baltimore, Md.)
|October 5, 2001
Summary
The FIC1 gene product functions as an ATP-dependent aminophospholipid translocase, crucial for maintaining membrane lipid asymmetry in liver and intestine. This transporter
Area of Science:
- Cell Biology
- Biochemistry
- Genetics
Background:
- Mutations in the FIC1 gene cause familial intrahepatic cholestasis I (Byler's disease) and benign recurrent intrahepatic cholestasis.
- The precise function of the FIC1 gene product in these cholestatic conditions remains incompletely understood.
Purpose of the Study:
- To investigate the localization and biochemical function of Fic1 in rat liver and intestine.
- To determine if Fic1 acts as an aminophospholipid translocase and its dependence on cellular energy.
Main Methods:
- Immunocytochemistry and immunoblotting to localize Fic1 protein in rat tissues.
- Biochemical assays of membrane fractions to measure aminophospholipid translocase activity.
- Transient transfection studies in CHOK1 cells to assess Fic1 function.
Main Results:
- Fic1 was localized to the canalicular plasma membrane in liver and the apical membrane in intestinal epithelial cells.
- Adenosine triphosphate (ATP)-dependent aminophospholipid (phosphatidylserine) translocase activity correlated with Fic1 presence.
- Transfection studies confirmed Fic1's role in energy-dependent phosphatidylserine translocation.
Conclusions:
- FIC1 encodes a canalicular P-type ATPase functioning as an energy-dependent aminophospholipid translocase.
- This transporter is critical for maintaining aminophospholipid distribution across the plasma membrane.
- Further research is needed to elucidate the role of this mechanism in cholestasis.
Related Concept Videos
01:27Liver Histology
The microscopic anatomy of the liver is a complex and intricate system that comprises numerous structural units known as liver lobules, each of which is comparable in size to a sesame seed. These hexagonal structures consist of plates of liver cells or hepatocytes, which are characterized by their versatility and abundance of cellular apparatus like rough and smooth ER, Golgi apparatus, peroxisomes, and mitochondria.
Hepatocytes perform a variety of essential functions. They secrete...
Hepatocytes perform a variety of essential functions. They secrete...
01:22Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess the...
01:24Cirrhosis II: Pathophysiology
Cirrhosis is a progressive chronic liver injury caused by prolonged inflammation, excessive fibrotic remodeling, and impaired regeneration. Over time, repeated hepatic insults disrupt the liver’s architecture and function, leading to reduced blood flow, impaired bile drainage, and diminished metabolic capacity.Pathophysiology of cirrhosisCirrhosis arises from three main responses to chronic liver damage: inflammation, immune activation, and hepatocyte death. These processes lead to structural...
01:25Jaundice
Jaundice, or icterus, is the yellow discoloration of the skin, sclerae, and mucous membranes. It happens when plasma bilirubin levels rise above 2.5-3 mg/dL, leading to bilirubin deposition in tissue.Bilirubin is a byproduct of hemoglobin degradation. In macrophages, hemoglobin breaks down into globin and heme. Globin is converted into amino acids, while heme is turned into biliverdin by heme oxygenase, which is then reduced to unconjugated bilirubin by biliverdin reductase.Unconjugated...
01:20Cholecystitis
Cholecystitis is inflammation of the gallbladder, most commonly caused by obstruction of the cystic duct. This blockage prevents bile from draining, leading to gallbladder distension, inflammation, and potentially serious complications. This condition may present acutely or chronically and can happen with or without gallstones.EtiologyAbout 95% of cholecystitis cases are calculous, caused by gallstones blocking the cystic duct, leading to bile accumulation and inflammation of the gallbladder...
01:21Chronic Pancreatitis II: Pathophysiology
Chronic pancreatitis is a progressive and irreversible inflammation of the pancreas, most often caused by long-term alcohol abuse, but it can also be related to ductal obstruction, smoking, or genetic factors.Chronic pancreatitis occurs when the pancreas is repeatedly exposed to harmful agents like alcohol, smoking, ductal obstruction, or genetic predisposition. These factors lead to the release of toxic metabolites and inflammatory cytokines, sustaining chronic inflammation in the pancreatic...