Linked Life Data

10553011

Source:http://linkedlifedata.com/resource/pubmed/id/10553011

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2000-1-19
pubmed:abstractText
There is no consensus whether hepatic lipid regulatory enzymes play primary or secondary roles in cholesterol cholelithiasis. We have used inbred mice with Lith genes that determine cholesterol gallstone susceptibility to evaluate the question. We studied activities of regulatory enzymes in cholesterol biosynthesis (HMG-CoA reductase), cholesterol esterification (acyl-CoA:cholesterol acyltransferase) and the "neutral" (cholesterol 7alpha-hydroxylase) and "acidic" (sterol 27-hydroxylase) pathways of bile salt synthesis in strains C57L/J and SWR/J as well as recombinant inbred (AKXL-29) mice, all of which have susceptible Lith alleles, and compared them to AKR/J mice with resistant Lith alleles. We determined hepatic enzyme activities of male mice before and at frequent intervals during feeding a lithogenic diet (15% dairy fat, 1% cholesterol, 0.5% cholic acid) for 12 weeks. Basal activities on chow show significant genetic variations for HMG-CoA reductase, sterol 27-hydroxylase, and acyl-CoA: cholesterol acyltranferase, but not for cholesterol 7alpha-hydroxylase. In response to the lithogenic diet, activities of the regulatory enzymes in the two bile salt synthetic pathways are coordinately down-regulated and correlate inversely with prevalence rates of cholesterol crystals and gallstones. Compared with gallstone-resistant mice, significantly higher HMG-CoA reductase activities together with lower activities of both bile salt synthetic enzymes are hallmarks of the enzymatic phenotype in mice with susceptible Lith alleles. The most parsimonious explanation for the multiple enzymatic alterations is that the primary Lith phenotype induces secondary events to increase availability of cholesterol to supply the sterol to the hepatocyte canalicular membrane for hypersecretion into bile.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-2275
pubmed:author
pubmed:issnType
Print
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2080-90
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10553011-Alleles, pubmed-meshheading:10553011-Animals, pubmed-meshheading:10553011-Bile, pubmed-meshheading:10553011-Cholelithiasis, pubmed-meshheading:10553011-Cholesterol, Dietary, pubmed-meshheading:10553011-Cholesterol 7-alpha-Hydroxylase, pubmed-meshheading:10553011-Cytochrome P-450 CYP27A1, pubmed-meshheading:10553011-Cytochrome P-450 Enzyme System, pubmed-meshheading:10553011-Diet, pubmed-meshheading:10553011-Gallbladder, pubmed-meshheading:10553011-Genetic Predisposition to Disease, pubmed-meshheading:10553011-Hydroxymethylglutaryl CoA Reductases, pubmed-meshheading:10553011-Liver, pubmed-meshheading:10553011-Male, pubmed-meshheading:10553011-Mice, pubmed-meshheading:10553011-Mice, Inbred AKR, pubmed-meshheading:10553011-Mice, Inbred C57BL, pubmed-meshheading:10553011-Mice, Inbred Strains, pubmed-meshheading:10553011-Phenotype, pubmed-meshheading:10553011-Steroid Hydroxylases, pubmed-meshheading:10553011-Sterol O-Acyltransferase, pubmed-meshheading:10553011-Time Factors
pubmed:year
1999
pubmed:articleTitle
Phenotypic characterization of Lith genes that determine susceptibility to cholesterol cholelithiasis in inbred mice: integrated activities of hepatic lipid regulatory enzymes.
pubmed:affiliation
Department of Medicine, Harvard Medical School, Gastroenterology Division, Brigham and Women's Hospital, and Harvard Digestive Diseases Center, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.