Modulation of intrahepatic cholesterol trafficking: evidence by in vivo antisense treatment for the involvement of sterol carrier protein-2 in newly synthesized cholesterol transport into rat bile

PUGLIELLI, L.; RIGOTTI, A.; AMIGO, L.; NUÑEZ, L.; GRECO, A. V.; SANTOS, M. J.; NERVI, F.

doi:10.1042/bj3310975u

Cited by 28 publications

(39 citation statements)

References 34 publications

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“…62 We propose that FABPL, in addition to SCP2, may be involved in hepatocellular cholesterol transport. This concept is supported by a recent study where diosgenin-induced cholesterol hypersecretion in rats was associated with hepatic up-regulation of SCP2 63 and FABPL. 64 Because FABPL levels in cytosol are by one or two orders of magnitude higher as compared with SCP2, 65,66 FABPL may contribute significantly to the transport of cholesterol.…”

Section: Discussionmentioning

confidence: 54%

Biliary cholesterol hypersecretion in gallstone-susceptible mice is associated with hepatic up-regulation of the high-density lipoprotein receptor SRBI

Fuchs¹,

Ivandic

Müller³

et al. 2001

Hepatology

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Enhanced hepatocellular trafficking of cholesterol to the bile canaliculus and cholesterol hypersecretion appears critical for gallstone formation. Therefore, we studied in more detail the hepatic cholesterol transport pathways in a mouse model of cholesterol gallstone disease. Biliary lipid secretion rates, plasma lipoprotein levels, hepatic expression of lipoprotein receptors, lipid regulatory enzymes, and putative cholesterol transporting proteins were analyzed in gallstone-susceptible C57L/J and gallstone-resistant AKR/J mice, which were fed a lithogenic diet. Biliary cholesterol hypersecretion in C57L mice was associated with decreased plasma high-density lipoprotein (HDL) cholesterol levels and significant hepatic induction of the HDL receptor (SRBI) and cholesteryl ester hydrolase. In response to the lithogenic diet, fatty-acid binding protein of liver (FABPL) was markedly induced in both mouse strains. Caveolin 1 was elevated only in plasma membranes of gallstone-susceptible C57L mice, which also failed to down-regulate cholesterol synthesis. These data suggest a role of the reverse cholesterol transport pathway for genetically determined gallstone susceptibility in the mouse. (HEPATOLOGY 2001;33: 1451-1459.)

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Section: Discussionmentioning

confidence: 54%

Biliary cholesterol hypersecretion in gallstone-susceptible mice is associated with hepatic up-regulation of the high-density lipoprotein receptor SRBI

Fuchs¹,

Ivandic

Müller³

et al. 2001

Hepatology

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show abstract

“…Liver samples were homogenized (38) followed by centrifugation at 100,000 g for 1 h to isolate the soluble (cytosolic) fraction. Western blot analyses were performed to determine protein expression levels of catalase, L-FABP, SCP-2, SCP-x, and PPAR ␣ .…”

Section: Western Blottingmentioning

confidence: 99%

“…Lipids were extracted from liver homogenates and serum (38) with n -hexane-2-propanol (3:2, v/v) (39,40) and divided into portions for mass and fatty acid composition determination. One half of each extracted lipid sample was resolved into individual lipid classes and identified by comparison with known standards using Silica gel G thin-layer chromatography plates developed in by guest, on May 11, 2018 www.jlr.org Downloaded from petroleum ether-diethyl ether-methanol-acetic acid (90:7:2:0.5) (39,40).…”

Section: Lipid Analysesmentioning

confidence: 99%

Sexually dimorphic metabolism of branched-chain lipids in C57BL/6J mice

Atshaves

Payne

McIntosh

et al. 2004

Journal of Lipid Research

118

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Despite the importance of branched chain lipid oxidation in detoxification, almost nothing is known regarding factors regulating peroxisomal uptake, targeting, and metabolism. One peroxisomal protein, sterol carrier protein-x (SCP-x), is thought to catalyze a key thiolytic step in branched chain lipid oxidation. When mice with substantially lower hepatic levels of SCP-x were tested for susceptibility to dietary stress with phytol (a phytanic acid precursor and peroxisome proliferator), livers of phytol-fed female but not male mice i ) accumulated phytol metabolites (phytanic acid, pristanic acid, and ⌬ -2,3-pristanic acid); ii ) exhibited decreased fat tissue mass and increased liver mass/ body mass; iii ) displayed signs of histopathological lesions in the liver; and iv ) demonstrated significant alterations in hepatic lipid distributions. Moreover, both male and female mice exhibited phytol-induced peroxisomal proliferation, as demonstrated by liver morphology and upregulation of the peroxisomal protein catalase. In addition, levels of liver fatty acid binding protein, along with SCP-2 and SCP-x, increased, suggesting upregulation mediated by phytanic acid, a known ligand agonist of the peroxisomal proliferator-activated receptor ␣ . In summary, the present work establishes a role for SCP-x in branched chain lipid catabolism and demonstrates a sexual dimorphic response to phytol, a precursor of phytanic acid, in lipid parameters and hepatotoxicity.

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“…Sterol carrier protein 2 (SCP2), also called nonspecific lipid transfer protein, is a 13.2 KD base protein and exists in peroxisomes, mitochondria, the endoplasmic reticulum and in the cytoplasm (5)(6)(7). In its role as a transporter, this protein participates in the transportation of cholesterol inside the cell and through the cytoplasm membrane, (8,9) as well as in the rapid transportation of newly synthesized cholesterol from the endoplasmic reticulum into bile without the intervention of the cytomicrotubule system and Golgi bodies (10). Additionally, some researchers indicate that it may have a role in the biosynthesis of cholesterol, (11)(12)(13) and in the transformation of cholesterol to bile acids (14,15), cholesterol esters (16) and sterols (17).…”

Section: Introductionmentioning

confidence: 99%

Increased bile lithogenicity by SCP2 via HMGCR and CYP7A1 regulation in human hepatocytes

Li²,

Zhao³

et al. 2013

Turk J Gastroenterol

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Modulation of intrahepatic cholesterol trafficking: evidence by in vivo antisense treatment for the involvement of sterol carrier protein-2 in newly synthesized cholesterol transport into rat bile

Cited by 28 publications

References 34 publications

Biliary cholesterol hypersecretion in gallstone-susceptible mice is associated with hepatic up-regulation of the high-density lipoprotein receptor SRBI

Biliary cholesterol hypersecretion in gallstone-susceptible mice is associated with hepatic up-regulation of the high-density lipoprotein receptor SRBI

Sexually dimorphic metabolism of branched-chain lipids in C57BL/6J mice

Increased bile lithogenicity by SCP2 via HMGCR and CYP7A1 regulation in human hepatocytes

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