Disease relevance of Scp2

• Scp2 deficiency did not prevent gallstone formation and may be compensated in part by hepatic up-regulation of liver fatty acid-binding protein [1].
• Our results suggest that overexpression of SCP2 contributes to biliary cholesterol hypersecretion and the pathogenesis of gallstones in genetically susceptible mice [2].
• Complete deficiency of SCP2 and SCPx was associated with marked alterations in gene expression, peroxisome proliferation, hypolipidemia, impaired body weight control, and neuropathy [3].
• We have cloned the cytosolic/peroxisomal form of mouse SCP-2 into the Escherichia coli expression vector pKK233-2 and have expressed and purified recombinant mouse SCP-2, Mr 13,034 [4].
• Recombinant adenovirus Ad.rSCP2 was used to overexpress SCP-2 in livers of mice [5].

High impact information on Scp2

• The defect became evident from up to 10-fold accumulation of the tetramethyl-branched fatty acid phytanic acid in Scp2(-/-) mice [3].
• Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function [3].
• These results corresponded to high-affinity binding of phytanoyl-CoA to the recombinant rat SCP2 protein, as well as high 3-ketopristanoyl-CoA thiolase activity of the recombinant rat SCPx protein [3].
• Sterol carrier protein 2 gene transfer changes lipid metabolism and enterohepatic sterol circulation in mice [6].
• However, addition of sterol carrier protein-2 in vitro significantly reduced the proportion of crystalline dehydroergosterol in the isolated lysosomes [7].

Chemical compound and disease context of Scp2

• Although expression of sterol carrier protein (SCP)-2, SCP-x, or liver FABP (L-FABP) in transfected L cells reduced [(3)H]phytanic acid uptake (57-87%) and lipid accumulation (21-27%), nevertheless [(3)H]phytanic acid oxidation was inhibited (74-100%) and phytanic acid toxicity was enhanced in the order L-FABP >> SCP-x > SCP-2 [8].

Biological context of Scp2

• Assignment of the mouse sterol carrier protein gene (Scp2) to chromosome 4 [9].
• In this report we show that a mouse cDNA (785 base pairs) encodes a precursor form of SCP-2 containing a N-terminal presequence and an additional C-terminal residue [4].
• In summary, these data showed for the first time that SCP-2 and SCP-x stimulate oxidation and esterification of branched-chain as well as straight-chain fatty acids in intact cells [10].
• These effects suggest a key regulatory role for SCP-2 in hepatic lipid metabolism and the existence of a reciprocal relationship between the fluxes of lipids across the sinusoidal and canalicular membranes [5].
• Cloning, expression and sequences of mouse sterol-carrier protein-x-encoding cDNAs and a related pseudogene [11].

Anatomical context of Scp2

• These signals are not found in SCP-2 purified from rat liver cytosol which is believed to be a cytosolic form [4].
• Sterol carrier protein-2/sterol carrier protein-x expression differentially alters fatty acid metabolism in L cell fibroblasts [10].
• Sterol carrier protein-2 selectively alters lipid composition and cholesterol dynamics of caveolae/lipid raft vs nonraft domains in L-cell fibroblast plasma membranes [12].
• Sterol carrier protein-2 expression alters plasma membrane lipid distribution and cholesterol dynamics [13].
• Sterol carrier protein-2 localization in endoplasmic reticulum and role in phospholipid formation [14].

Associations of Scp2 with chemical compounds

• We hypothesized that Scp2 deficiency may alter biliary lipid secretion and hepatic cholesterol metabolism [1].
• Early reports indicates cross-reactivity of brain proteins with antisera against two native liver sterol transfer proteins, sterol carrier protein-2 (SCP-2) and the liver form of fatty acid-binding protein (L-FABP) [15].
• Our results demonstrate that the SCPx thiolase is critical for beta-oxidation of the steroid side chain in conversion of cholesterol into bile acids [16].
• Recently, gene targeting of the SCP2/SCPx gene has shown in mice that the SCPx beta-ketothiolase is involved in peroxisomal beta-oxidation of 2-methyl-branched chain fatty acids like pristanic acid [16].
• In contrast, SCP-2 increased biliary lipid secretion and the proportion of hydrophobic PC molecular species in bile [5].

Physical interactions of Scp2

• Sterol carrier protein-2 directly interacts with caveolin-1 in vitro and in vivo [17].

Other interactions of Scp2

• These effects differed markedly from those of [(3)H]palmitic acid, whose uptake, oxidation, and induction of lipid accumulation were not reduced by L-FABP, SCP-2, or SCP-x expression [8].
• (v) Cytoplasmic LCFA-CoA binding proteins such as acyl-CoA binding protein, sterol carrier protein-2, and liver-FA binding protein slowed the process of 16:1-CoA degradation proportional to their respective affinities for this ligand [18].
• However, only expression of the 15 kDa pro-SCP-2 increased the cytoplasmic diffusion of the fluorescent fatty acid [19].
• Using the northern blot technique, the steady-state levels for the mRNAs encoding acyl-CoA oxidase, pristanoyl-CoA oxidase, trans2, 3enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase multifunctional enzyme type 2, 3-ketoacyl-CoA thiolase and sterol-carrier-protein x during postnatal brain development were measured [20].
• Thus, in the presence of nonspecific lipid transfer protein, the lipid composition of the membrane where sialyltransferase is located was modified to resemble the lipid composition of the liposomes [21].

Analytical, diagnostic and therapeutic context of Scp2

• Structure and chromosomal assignment of the murine sterol carrier protein 2 gene (Scp2) and two related pseudogenes by in situ hybridization [22].
• Indirect immunofluorescence double labeling and laser scanning confocal microscopy detected SCP-2 in peroxisomes > endoplasmic reticulum > mitochondria > lysosomes [14].
• Southern blotting showed that SCPx is likely to be encoded by a single-copy gene [23].

References