Characterization of liver disease and lipid metabolism in the Niemann-Pick C1 mouse.

Characterization of liver disease and lipid metabolism in the Niemann-Pick C1 mouse. Research Abstract Details 

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Characterization of liver disease and lipid metabolism in the Niemann-Pick C1 mouse. Abstract Text:

William S Garver,David Jelinek,Janice N Oyarzo,James Flynn,Matthew Zuckerman,Kumar Krishnan,Byung H Chung,Randall A Heidenreich,

Niemann-Pick type C1 (NPC1) disease is an autosomal-recessive cholesterol-storage disorder characterized by liver dysfunction, hepatosplenomegaly, and progressive neurodegeneration. The NPC1 gene is expressed in every tissue of the body, with liver expressing the highest amounts of NPC1 mRNA and protein. A number of studies have now indicated that the NPC1 protein regulates the transport of cholesterol from late endosomes/lysosomes to other cellular compartments involved in maintaining intracellular cholesterol homeostasis. The present study characterizes liver disease and lipid metabolism in NPC1 mice at 35 days of age before the development of weight loss and neurological symptoms. At this age, homozygous affected (NPC1(-/-)) mice were characterized with mild hepatomegaly, an elevation of liver enzymes, and an accumulation of liver cholesterol approximately four times that measured in normal (NPC1(+/+)) mice. In contrast, heterozygous (NPC1(+/-)) mice were without hepatomegaly and an elevation of liver enzymes, but the livers had a significant accumulation of triacylglycerol. With respect to apolipoprotein and lipoprotein metabolism, the results indicated only minor alterations in NPC1(-/-) mouse serum. Finally, compared to NPC1(+/+) mouse livers, the amount and processing of SREBP-1 and -2 proteins were significantly increased in NPC1(-/-) mouse livers, suggesting a relative deficiency of cholesterol at the metabolically active pool of cholesterol located at the endoplasmic reticulum. The results from this study further support the hypothesis that an accumulation of lipoprotein-derived cholesterol within late endosomes/lysosomes, in addition to altered intracellular cholesterol homeostasis, has a key role in the biochemical and cellular pathophysiology associated with NPC1 liver disease.

Characterization of liver disease and lipid metabolism in the Niemann-Pick C1 mouse. Publishing Authors By Initials

WS Garver,D Jelinek,JN Oyarzo,J Flynn,M Zuckerman,K Krishnan,BH Chung,RA Heidenreich,

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Characterization of liver disease and lipid metabolism in the Niemann-Pick C1 mouse. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of cellular biochemistry

VOLUME: 101

Page Numbers: 498-516

Journal Abbreviation:

ISSN: 0730-2312

DAY: 15

MONTH: May

YEAR: 2007

Characterization of liver disease and lipid metabolism in the Niemann-Pick C1 mouse. Information

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LANGUAGE: eng

NlmUniqueID: 8205768

Characterization of liver disease and lipid metabolism in the Niemann-Pick C1 mouse. Keywords Mesh Terms:

KEYWORDS: Sterol Regulatory Element Binding Protei

MESH TERMS: metabolism

Chemical & Substance for Abstract: Characterization of liver disease and lipid metabolism in the Niemann-Pick C1 mouse. Information

Substance Name: Cholesterol

Registry Number: 57-88-5

Grant and Affiliation Information for Characterization of liver disease and lipid metabolism in the Niemann-Pick C1 mouse.

AFFILIATION: Department of Pediatrics, The University of Arizona, Tucson, AZ 85724, USA. wgarver@peds.arizona.edu

Country: United States

AGENCY: United States NIDDK

GRANT: R21 DK071544-01

ACRONYM: DK

MEDLINETA: J Cell Biochem

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