Abstract:
BACKGROUND & AIMS:Progressive familial intrahepatic cholestasis can be caused by mutations in ABCB4 or ATP8B1; each encodes a protein that translocates phospholipids, but in opposite directions. ABCB4 flops phosphatidylcholine from the inner to the outer leaflet, where it is extracted by bile salts. ATP8B1, in complex with the accessory protein CDC50A, flips phosphatidylserine in the reverse direction. Abcb4(-/-) mice lack biliary secretion of phosphatidylcholine, whereas Atp8b1-deficient mice have increased excretion of phosphatidylserine into bile. Each system is thought to have a role protecting the canalicular membrane from bile salts. METHODS:To investigate the relationship between the mechanisms of ABCB4 and ATP8B1, we expressed the transporters separately and together in cultured cells and studied viability and phospholipid transport. We also created mice with disruptions in ABCB4 and ATP8B1 (double knockouts) and studied bile formation and hepatic damage in mice fed bile salts. RESULTS:Overexpression of ABCB4 was toxic to HEK293T cells; the toxicity was counteracted by coexpression of the ATP8B1-CDC50A complex. In Atp8b1-deficient mice, bile salts induced extraction of phosphatidylserine and ectoenzymes from the canalicular membrane; this process was not observed in the double-knockout mice. CONCLUSIONS:ATP8B1 is required for hepatocyte function, particularly in the presence of ABCB4. This is most likely because the phosphatidylserine flippase complex of ATP8B1-CDC50A counteracts the destabilization of the membrane that occurs when ABCB4 flops phosphatidylcholine. Lipid asymmetry is therefore important for the integrity of the canalicular membrane; ABCB4 and ATP8B1 cooperate to protect hepatocytes from bile salts.
journal_name
Gastroenterologyjournal_title
Gastroenterologyauthors
Groen A,Romero MR,Kunne C,Hoosdally SJ,Dixon PH,Wooding C,Williamson C,Seppen J,Van den Oever K,Mok KS,Paulusma CC,Linton KJ,Oude Elferink RPdoi
10.1053/j.gastro.2011.07.042subject
Has Abstractpub_date
2011-11-01 00:00:00pages
1927-37.e1-4issue
5eissn
0016-5085issn
1528-0012pii
S0016-5085(11)01075-4journal_volume
141pub_type
杂志文章相关文献
GASTROENTEROLOGY文献大全abstract::A primary malignant melanoma of the gallbladder, metastatic to the common bile duct, is reported. Both tumor sites were first visualized by abdominal sonography. The presence of the common bile duct metastasis was confirmed by endoscopic retrograde cholangiopancreatography. Histologic evidence is presented that the pr...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(86)90461-0
更新日期:1986-07-01 00:00:00
abstract::Adverse effects associated with nonsteroidal antiinflammatory drug treatment are reported more commonly to regulatory authorities than the adverse effects of any other form of treatment. Epidemiologic evidence in general suggests a doubling or quadrupling of the risk of ulcer complications or death in recipients of su...
journal_title:Gastroenterology
pub_type: 杂志文章,评审
doi:10.1016/s0016-5085(89)80060-5
更新日期:1989-02-01 00:00:00
abstract::An increased risk of esophageal carcinoma has been reported in systemic sclerosis (scleroderma). Periodic endoscopic or radiologic surveillance, or both, of systemic sclerosis patients with gastroesophageal reflux symptoms has been recommended for early detection of Barrett's mucosa and esophageal adenocarcinoma. A re...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(85)90440-8
更新日期:1985-09-01 00:00:00
abstract:BACKGROUND & AIMS:Helicobacter pylori is believed to predispose to gastric cancer by inducing gastric atrophy and hypochlorhydria. First-degree relatives of patients with gastric cancer have an increased risk of developing gastric cancer. The aim of this study was to determine the prevalence of atrophy and hypochlorhyd...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/s0016-5085(00)70410-0
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND AND AIMS:The MDR1 gene encodes P-glycoprotein 170, an efflux transporter that is highly expressed in intestinal epithelial cells. The MDR1 exonic single nucleotide polymorphisms (SNPs) C3435T and G2677T have been shown to correlate with activity/expression of P-glycoprotein 170. METHODS:This was a case-cont...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2004.11.019
更新日期:2005-02-01 00:00:00
abstract::The effect of continuous intraduodenal enteral nutrition on gastric pH was compared with the effects of fasting and of parenteral and standard nutrition control regimens containing equal amounts of carbohydrate, protein, and lipid. Eleven healthy volunteers underwent four 24-hour intragastric pH-metry studies; serum g...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(92)91708-c
更新日期:1992-05-01 00:00:00
abstract:BACKGROUND & AIMS:Mutational inactivation of adenomatous polyposis coli (APC) is an early event in colorectal cancer (CRC) progression that affects the stability and increases the activity of β-catenin, a mediator of Wnt signaling. Progression of CRC also involves inactivation of signaling via transforming growth facto...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2011.11.026
更新日期:2012-03-01 00:00:00
abstract:BACKGROUND & AIMS:The natural history and management of pancreatic cysts, especially for branch duct intraductal papillary mucinous neoplasms (BD-IPMNs), remain uncertain. We developed evidence-based nomograms to assist with clinical decision making. METHODS:We used decision analysis with Markov modeling to compare co...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2009.10.001
更新日期:2010-02-01 00:00:00
abstract:BACKGROUND & AIMS:Hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease. Interferon-α (IFNα) is an important component of anti-HCV therapy; it up-regulates transcription of IFN-stimulated genes, many of which have been investigated for their antiviral effects. However, all of the genes require...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2013.02.026
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND & AIMS:In several rat infection experiments, we have shown that dietary calcium inhibits intestinal colonization and translocation of invasive salmonella. The aim of the present study was to find out whether calcium is also protective against enterotoxigenic Escherichia coli (ETEC) infection. This was first ...
journal_title:Gastroenterology
pub_type: 临床试验,杂志文章
doi:10.1016/s0016-5085(03)00884-9
更新日期:2003-08-01 00:00:00
abstract::Eleven infants born to mothers with acute hepatitis B during the third trimester of pregnancy who were hepatitis B surface antigen-positive at delivery were treated with hepatitis B immune globulin within 24-48 h of birth. Five infants received one dose of hepatitis B immune globulin and 6 infants received a second do...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(85)90757-7
更新日期:1985-07-01 00:00:00
abstract:BACKGROUND & AIMS:Persons infected with Helicobacter pylori show an enhanced meal-stimulated gastrin release compared with uninfected controls. The aim of this study was to determine in animal models whether this gastrin release could be related to chronic gastric inflammation, elevated luminal ammonia level, or a comb...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/gast.1996.v110.pm8608890
更新日期:1996-03-01 00:00:00
abstract:BACKGROUND & AIMS:Human tumors and liver cancer cell lines express the product of a fusion between the first 13 exons in the mannosidase α class 2A member 1 gene (MAN2A1) and the last 6 exons in the FER tyrosine kinase gene (FER), called MAN2A1-FER. We investigated whether MAN2A1-FER is expressed by human liver tumors ...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2016.12.036
更新日期:2017-10-01 00:00:00
abstract::The short-term effects of rat pancreatic duct obstruction were evaluated and compared with those recently reported to follow obstruction of the rabbit pancreatic duct. In both species pancreatic edema and hyperamylasemia are noted, and the lysosomal hydrolase cathepsin B is redistributed from the lysosome-enriched to ...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(91)90601-g
更新日期:1991-01-01 00:00:00
abstract:BACKGROUND & AIMS:The adenoma detection rate (ADR) is an important quality indicator of screening colonoscopy; it is inversely associated with risk of interval cancers and colorectal cancer mortality. We assessed trends in the ADR in the first 10 years of the German screening colonoscopy program. METHODS:We calculated...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2015.04.012
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND & AIMS:Lamivudine inhibits hepatitis B virus replication. This study investigated 6 months of lamivudine treatment at three doses. METHODS:Fifty-one patients (43% white, 49% Asian) with chronic hepatitis B were randomly assigned to receive 25, 100, or 300 mg of lamivudine orally once daily for 24 weeks with...
journal_title:Gastroenterology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1053/gast.1997.v113.pm9322520
更新日期:1997-10-01 00:00:00
abstract::We have examined the possibility that the 33- and 39-amino acid forms of cholecystokinin (CCK) are cleaved to produce CCK-octapeptide (CCK-8) during circulation in humans. When a mixture of the 33- and 39-amino acid forms of porcine CCK was infused at 0.1-2.5 pmol/kg.min into normal subjects, material indistinguishabl...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(88)90303-4
更新日期:1988-07-01 00:00:00
abstract:BACKGROUND & AIMS:Approximately half of the families that fulfill Amsterdam criteria for Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) do not have evidence of the germline mismatch repair gene mutations that define this syndrome and result in microsatellite instability (MSI). The carcinogenic path...
journal_title:Gastroenterology
pub_type: 杂志文章,多中心研究
doi:10.1053/j.gastro.2010.01.035
更新日期:2010-05-01 00:00:00
abstract::Noninvasive imaging modalities may suggest the diagnosis of Budd-Chiari syndrome but they are rarely diagnostic. Inferior vena cavography, hepatic venography, and liver biopsy, alone or in combination, are usually necessary for definitive diagnosis. Because of its excellent depiction of blood vessels as regions of abs...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/s0016-5085(86)80029-4
更新日期:1986-11-01 00:00:00
abstract:BACKGROUND & AIMS:Simeprevir (TMC435) is an oral NS3/4 protease inhibitor in phase III trials for chronic hepatitis C virus (HCV) infection. We performed a phase IIb, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of the combination of simeprevir, peginterferon-α2a (PegIFN), and ...
journal_title:Gastroenterology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1053/j.gastro.2013.10.058
更新日期:2014-02-01 00:00:00
abstract::Pancreatitis is a common disorder with significant morbidity and mortality, yet little is known about its pathogenesis, and there is no specific or effective treatment. Its development involves dysregulated autophagy and unresolved inflammation, demonstrated by studies in genetic and experimental mouse models. Disease...
journal_title:Gastroenterology
pub_type: 杂志文章,评审
doi:10.1053/j.gastro.2017.08.071
更新日期:2017-11-01 00:00:00
abstract:BACKGROUND & AIMS:Previous research has yielded conflicting data as to whether the natural history of inflammatory bowel disease follows a seasonal pattern. The purpose of this study was to determine whether relapse of inflammatory bowel disease follows a seasonal pattern either across a cohort of patients or within in...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2003.12.003
更新日期:2004-03-01 00:00:00
abstract::We studied the appearance of specific secretory immunoglobulin A (IgA) antibody in bile after inoculation of live Giardia lamblia trophozoites into rat intestine. Serial bile specimens collected before and after inoculation of trophozoites were assayed for IgA antibodies by indirect immunofluorescence. Secretory IgA a...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:
更新日期:1984-11-01 00:00:00
abstract:BACKGROUND & AIMS:Sex hormones have been reported to modulate visceral hypersensitivity (VH). Estrogen regulates neurons not only by binding to estrogen receptors (ERalpha and ERbeta) to initiate transcription but also via the G-protein coupled receptor GPR30, which binds and rapidly mediates actions of estrogen. We ex...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2009.03.047
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND & AIMS:Patients with sphincter of Oddi dysfunction are at high risk of developing pancreatitis after endoscopic biliary sphincterotomy. Impaired pancreatic drainage caused by pancreatic sphincter hypertension is the likely explanation for this increased risk. A prospective, randomized controlled trial was co...
journal_title:Gastroenterology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0016-5085(98)70031-9
更新日期:1998-12-01 00:00:00
abstract:BACKGROUND & AIMS:During severe pancreatitis, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha are produced in large quantities. The aim of this study was to determine whether either one plays a more dominant role and if their detrimental effects are additive. METHODS:Necrotizing pancreatitis was induced i...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/gast.1997.v113.pm9352880
更新日期:1997-11-01 00:00:00
abstract:BACKGROUND & AIMS:Abdominal bloating is a frequent complaint in irritable bowel syndrome (IBS), but its underlying mechanism remains uncertain. Our aim was to determine whether the abdominal wall, specifically its adaptation to intra-abdominal volumes, plays a role. METHODS:In 12 patients complaining of abdominal bloa...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2005.12.036
更新日期:2006-04-01 00:00:00
abstract:BACKGROUND & AIMS:There have been conflicting results on a cell of origin in pancreatic regeneration. These discrepancies predominantly stem from lack of specific markers for the pancreatic precursors/stem cells, as well as differences in the targeted cells and severity of tissue injury in the experimental models so fa...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/j.gastro.2011.07.003
更新日期:2011-10-01 00:00:00
abstract:BACKGROUND/AIMS:Reflex relaxation is a mechanism whereby the colon can show short-term dilatation in the absence of mechanical obstruction. This study investigated the tonic response of the canine colon to ileal distention and its pharmacological control. METHODS:In four dogs, the tone of the proximal colon was record...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1016/0016-5085(94)90692-0
更新日期:1994-03-01 00:00:00
abstract:BACKGROUND & AIMS:Previous studies indicated that the peptide neurotensin (NT) stimulates Cl(-) secretion in animal small intestinal mucosa in vitro. In this study, we investigated whether NT causes Cl(-) secretion in human colonic mucosa and examined the mechanism of this response. METHODS:Human mucosal preparations ...
journal_title:Gastroenterology
pub_type: 杂志文章
doi:10.1053/gast.2000.9310
更新日期:2000-08-01 00:00:00