Sterol carrier protein 2 gene transfer changes lipid metabolism and enterohepatic sterol circulation in mice

Zanlungo, Silvana; Amigo, Ludwig; Mendoza, Hegaly; Miquel, Juan Francisco; Vío, Carlos P.; Glick, Jane M.; Rodríguez, Annabelle; Kozarsky, Karen; Quiñones, Verónica; Rigotti, Attilio; Nervi, Flavio

doi:10.1053/gast.2000.20198

Cited by 34 publications

(49 citation statements)

References 55 publications

(59 reference statements)

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“…10,47,60,61 Utilizing proteomic analysis, we identified SCP2 as the transfer protein in itraconazole-mediated cholesterol trafficking. SCP2, also called nonspecific lipid transfer protein, enhances cholesterol transfer out of the lysosomal membrane, as well as the regulation of multiple lipid signaling pathways in the plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

Itraconazole suppresses the growth of glioblastoma through induction of autophagy

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Itraconazole suppresses the growth of glioblastoma through induction of autophagy

et al. 2014

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“…The ability of SCP-2 to bind cholesterol is well established (52). Overexpression of SCP-2 in L cells inhibited cholesterol efflux and increased the intracellular cholesterol pool (53), and adenoviral overexpression of SCP-2 was previously found to increase hepatic cholesterol contents (54). Conversely, liver cholesterol ester levels are reduced by 50% in SCP-2/SCP-x null mice (49) along with hypersecretion of cholesterol in bile (17,50,51).…”

Section: Discussionmentioning

confidence: 99%

Decreased Liver Fatty Acid Binding Capacity and Altered Liver Lipid Distribution in Mice Lacking the Liver Fatty Acid-binding Protein Gene

Martin

Danneberg

Kumar

et al. 2003

Journal of Biological Chemistry

156

183

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Although liver fatty acid-binding protein (L-FABP) isan important binding site for various hydrophobic ligands in hepatocytes, its in vivo significance is not understood. We have therefore created L-FABP null mice and report here their initial analysis, focusing on the impact of this mutation on hepatic fatty acid binding capacity, lipid composition, and expression of other lipid-binding proteins. Gel-filtered cytosol from L-FABP null liver lacked the main fatty acid binding peak in the fraction that normally comprises both L-FABP and sterol carrier protein-2 (SCP-2). The binding capacity for cis-parinaric acid was decreased >80% in this region. Molar ratios of cholesterol/cholesterol ester, cholesteryl ester/triglyceride, and cholesterol/phospholipid were 2-to 3-fold greater, reflecting up to 3-fold absolute increases in specific lipid classes in the order cholesterol > cholesterol esters > phospholipids. In contrast, the liver pool sizes of nonesterified fatty acids and triglycerides were not altered. However, hepatic deposition of a bolus of intravenously injected family (1-3), is found in the liver, intestine, and kidney, but only in liver is it not co-expressed with other members of its family. L-FABP is known to bind fatty acids and various other hydrophobic molecules, although its actual contribution to the lipid-binding capacity of liver cytosol is not known. Given that L-FABP is expressed at very high levels (2-5% of cytosolic protein) in the differentiated hepatocyte (4, 5) and that these levels correlate well with lipid metabolism (2), it can be speculated that L-FABP contributes considerably to hepatic lipidbinding and lipid metabolism. Work with cell-free systems and transfected cells has further strengthened this view. For example, in cell-free preparations L-FABP was shown to stimulate the esterification of oleic acid while inhibiting that of palmitic acid (6). L cells overexpressing L-FABP show increased rates of fatty acid uptake and esterification (7) as well as increased contents of phospholipid and cholesterol esters (8, 9). HepG2 hepatoma cells expressing an L-FABP antisense RNA showed a dose-dependent reduction of fatty acid uptake (10). Furthermore, overexpression of L-FABP in McA-RH7777 hepatoma cells incubated with palmitic acid decreased the synthesis and secretion of triglycerides while increasing beta oxidation and the secretion of apolipoprotein B100 (11). Thus, the various in vitro systems have allowed researchers to propose specific functions of L-FABP in vivo.However, in vitro studies of FABPs have inherent limitations. The only firmly established function of FABPs is the reversible binding of hydrophobic ligands, and these proteins do not exhibit any enzymatic function or energy requirement. This suggests that these proteins play passive (facilitative) roles that, almost by definition, are strongly dependent on the cellular context. One context of the highly expressed L-FABP is the highly differentiated hepatocyte, a cell type featuring an intense lipid metabolism that is not eas...

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“…Both ABCG5 (Ϫ76%) and ABCG8 (Ϫ66%) were down-regulated in the liver of FXR(Ϫ/Ϫ) compared with wild-type mice. The expression of the cholesterol ester hydrolase (CEH), an enzyme responsible for the conversion (34) of intra-cellular CE into FC and of the sterol carrier protein (SCP), a protein thought to be involved in the hepatocellular trafficking of FC to the canalicular membrane (35,36) were also reduced in the liver of FXR(Ϫ/Ϫ) mice (Fig. 4a).…”

Section: Synthesis Of Apolipoprotein B-containing Lipoprotein (Lpb) Imentioning

confidence: 99%

The Farnesoid X-receptor Is an Essential Regulator of Cholesterol Homeostasis

Lambert¹,

Amar²,

Guo³

et al. 2003

Journal of Biological Chemistry

348

265

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Sterol carrier protein 2 gene transfer changes lipid metabolism and enterohepatic sterol circulation in mice

Cited by 34 publications

References 55 publications

Itraconazole suppresses the growth of glioblastoma through induction of autophagy

Itraconazole suppresses the growth of glioblastoma through induction of autophagy

Decreased Liver Fatty Acid Binding Capacity and Altered Liver Lipid Distribution in Mice Lacking the Liver Fatty Acid-binding Protein Gene

The Farnesoid X-receptor Is an Essential Regulator of Cholesterol Homeostasis

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