Sterol Carrier and Lipid Transfer Proteins

Vahouny, George V.; Chanderbhan, Ronald; Kharroubi, Akram; Noland, B.J.; Pastuszyn, Andrzej; Scallen, Terence J.

doi:10.1016/b978-0-12-024922-0.50007-2

Cited by 93 publications

(57 citation statements)

References 115 publications

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“…However, the saturated FAs (phytanic acid and palmitic acid) were poorly targeted to CEs. This was opposite to the effect of SCP-2 and SCP-x on incorporation of unsaturated FA (oleic acid) into CEs in vitro (1,45,73,74) and in intact cells (2,19). Thus, while incorporation into TGs was stimulated, SCP-2 and SCP-x did not appear to enhance incorporation of saturated FAs (regardless of whether they were branched or nonbranched) into CEs.…”

Section: Discussionmentioning

confidence: 48%

Sterol carrier protein-2/sterol carrier protein-x expression differentially alters fatty acid metabolism in L cell fibroblasts

Atshaves

Storey

Schroeder

2003

Journal of Lipid Research

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Sterol carrier protein-2 (SCP-2) and SCP-x are ubiquitous proteins found in all mammalian tissues. Although both proteins interact with fatty acids, their relative contributions to the uptake, oxidation, and esterification of straight-chain (palmitic) and branched-chain (phytanic) fatty acids in living cells has not been resolved. Therefore, the effects of each gene product on fatty acid metabolism was individually examined. Based on the following, SCP-2 and SCP-x did not enhance the uptake/translocation of fatty acids across the plasma membrane into the cell: i ) a 2-fold increase in phytanic and palmitic acid uptake was observed at long incubation times in SCP-2-and SCP-x-expressing cells, but no differences were observed at initial time points; ii ) uptake of 2-bromo-palmitate, a nonoxidizable, poorly metabolizable fatty acid analog, was unaffected by SCP-2 or SCP-x overexpression; and iii ) SCP-2 and SCP-x expression did not increase targeting of radiolabeled phytanic and palmitic acid to the unesterified fatty acid pool. Moreover, SCP-2 and SCP-x expression enhanced fatty acid uptake by stimulating the intracellular metabolism via fatty acid oxidation and esterification. 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. 1)]. More recent studies indicate that SCP-2 also functions in the uptake and esterification of straight-chain (e.g., oleic acid) fatty acids (FAs) (2), while SCP-x participates in the oxidation of branchedchain (e.g., phytanic acid) FAs (3, 4). However, almost nothing is known about the function of SCP-x in FA uptake or esterification. Likewise, the relative roles of SCP-2 versus SCP-x in straight-chain or branched-chain FA oxidation remain unresolved. Despite the lack of conclusive evidence, several observations point to an important role for SCP-2 and SCP-x in functioning in these capacities, including FA binding affinities where SCP-2 binds straightchain FAs (5-11) and their metabolically active fatty acyl CoA derivatives (9, 12) to a high degree, as exhibited by K d s in the submicromolar and nM range, respectively. In addition, SCP-2 also binds branched-chain FAs such as phytanic or pristanic acid (9), as well as their respective acyl CoAs with high affinity (7, 9).The intracellular localization of SCP-x and SCP-2 also indicate a role in FA metabolism. The highest concentration of SCP-2 and SCP-x is in peroxisomes (13), where ␣ -oxidation of branched-chain FAs as well as the ␤ -oxidation of some straight chain FAs occurs (14-16). Additionally, it has been shown that half or more of total SCP-2 is extraperoxisomal (13, 17), where part of the SCP-2 may arise from the partial posttranslational cleavage of the SCP-x protein (18,19). Extraperoxisomal SCP-2 locations include: i ) plasma membrane in caveolae, wherein several FA translocase/transporter proteins reside (20); ii ) cytoplasm, where SCP-2 enhances diffusion of fluorescent fatty acid (21); ii...

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Section: Discussionmentioning

confidence: 48%

Sterol carrier protein-2/sterol carrier protein-x expression differentially alters fatty acid metabolism in L cell fibroblasts

Atshaves

Storey

Schroeder

2003

Journal of Lipid Research

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“…The mitochondrial phosphoprotein pp3O and its two precursor proteins, pp37 and pp32, have been shown to be produced in response to trophic hormones (34); however, no evidence is available that these polypeptides may function in the regulation ofadrenal steroidogenesis. The sterol carrier protein 2 (SCP2) is known to stimulate side-chain cleavage activity in adrenal mitochondria (35), but its adrenal level fails to change after ACTH stimulation (37). Finally, although the biological significance of these peptides-cannot be completely disregarded, no interaction between them and a high-affinity mitochondrial receptor has been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

“…Although a number of adrenal peptides have been proposed as regulators of mitochondrial cholesterol translocation (33)(34)(35), the biological significance of some of these factors is still unclear. For example, despite an initial report on the ability of the steroidogenesis activator polypeptide (SAP) to stimulate cholesterol side-chain cleavage in isolated adrenal mitochondria (33), the magnitude of this effect was relatively small (36).…”

Section: Discussionmentioning

confidence: 99%

Diazepam-binding inhibitor (DBI)-processing products, acting at the mitochondrial DBI receptor, mediate adrenocorticotropic hormone-induced steroidogenesis in rat adrenal gland.

Cavallaro

Korneyev

Guidotti³

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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Diazepam-binding inhibitor (DBI) is a 9-kDa polypeptide that colocalizes in glial, adrenocortical, and Leydig cells with the mitochondrial DBI receptor (MDR). By binding with high affinity to the MDR, DBI and one of its processing products-DBI-(17-50)-regulate pregnenolone synthesis and have been suggested to participate in the immediate activation of adrenal steroidogenesis by adrenocorticotropic hormone (ACTH). In adrenals of hypophysectomized rats (1 day after surgery), ACTH failed to acutely affect the amount of adrenal DBI and the density of MDR but increased the rate of DBI processing, as determined by the HPLC proffle of DBI-(17-50)-like immunoreactivity. The similar latency times for this effect and for ACTH stimulation of adrenal steroidogenesis suggest that the two processes are related. The ACTH-induced increase in both adrenal steroidogenesis and rate of DBI processing were completely inhibited by cycloheximide; this result suggests the requirement for the de novo synthesis of a protein with a short half-life, probably an endopeptidase. This enzyme, under the influence of ACTH, may activate formation of a DBI-processing product that stimulates steroidogenesis via the MDR. In support of this hypothesis is the demonstration that in hypophysectomized rats the MDR antagonist PK 11195 1-(2-chlorophenyl)-N-methyl-N-(l-methylpropyl)-3-isoquinolinecarboxamide completely inhibited the adrenal steroldogenesis stimulated by ACTH and by the high-affinity MDR lgand 4'-chlorodiazepam.The rate-limiting step in steroid biosynthesis is the conversion of cholesterol to pregnenolone. This reaction is catalyzed by the side-chain cleavage enzyme cytochrome P-450 [P-450SC; cholesterol, reduced-adrenal-ferredoxin:oxygen oxidoreductase (side-chain-cleaving), EC 1.14.15.6], which is located on the inner mitochondrial membrane (1). Several laboratories have established that it is the rate at which cholesterol is transported to the inner mitochondrial membrane, and not P-450SCC activity itself, that limits the rate of pregnenolone synthesis (2-5). The transfer of cholesterol to P-450,c, therefore, must be facilitated to achieve maximal rates of pregnenolone synthesis. The protein synthesis inhibitor cycloheximide has been shown to block the induction of steroidogenesis by adrenocorticotropic hormone (ACTH) (6)(7)(8), and this block appears to occur at the level of cholesterol transport from the outer to the inner mitochondrial membrane. It is believed that one or more proteins with a rapid turnover rate are required to effect cholesterol translocation within mitochondria and that ACTH may either increase the concentration of these proteins or activate them posttranslationally.A receptor that is located on the outer mitochondrial membrane and that is enriched in the mitochondria of steroidogenic cells participates in the regulation of intramitochondrial cholesterol transport and may mediate the immediate action of steroidogenic hormones, such as ACTH and human chorionic gonadotropin (9-12). Because diazepambinding ...

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“…Recent studies have suggested that this sterol translocation may be mediated by specific sterol transfer proteins. Sterol carrier protein 2 (SCP2), also called nonspecific lipid transfer protein (7), is a low molecular weight protein (13.2 kD) and thought to be one of highly touted candidates for an intracellular cholesterol carrier (6)(7)(8). SCP2 has been reported to facilitate enzymatic reactions involved in cholesterol biosynthesis in the liver (6), and in ACAT-catalyzed cholesterol esterification in various tissues such as the liver, intestine, adrenal cortex, and aorta (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Regulation of sterol carrier protein 2 (SCP2) gene expression in rat peritoneal macrophages during foam cell formation. A key role for free cholesterol content.

Hirai¹,

Kino²,

Tokinaga³

et al. 1994

J. Clin. Invest.

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Sterol carrier protein 2 (SCP2) has been shown to be involved in intracellular transport and metabolism of cholesterol. However, there have been no reports concerning SCP2 in macrophages, the major source of atheromatous foam cells. We investigated whether SCP2 is present in rat peritoneal macrophages and determined the changes of SCP2 and its mRNA levels in macrophages during foam cell formation induced by acetylated LDL (AcLDL).Immunoblot analysis and Northern blot analysis demonstrated that both SCP2 and its mRNA are expressed in rat peritoneal macrophages. Incubations with AcLDL caused a dose-and time-dependent increase of cellular esterified cholesterol, SCP2 and its mRNA in rat peritoneal macrophages. The inhibitor of acyl-CoA:cholesterol acyltransferase further enhanced AcLDL-induced increase of SCP2 protein and its mRNA. Incubations with 25-hydroxy cholesterol also caused a dose-dependent stimulation of SCP2 gene expression in macrophages, while incubation with maleylated BSA had no effect. These results suggest that the increment of cellular-free cholesterol is responsible for enhanced SCP2 gene expression in macrophages. The enhancement of SCP2 gene expression by AcLDL suggests that SCP2 may play an important role during foam cell formation induced by AcLDL which may be most important step for the atherosclerosis. (J. Clin. Invest. 1994. 94:2215-2223

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Sterol Carrier and Lipid Transfer Proteins

Cited by 93 publications

References 115 publications

Sterol carrier protein-2/sterol carrier protein-x expression differentially alters fatty acid metabolism in L cell fibroblasts

Sterol carrier protein-2/sterol carrier protein-x expression differentially alters fatty acid metabolism in L cell fibroblasts

Diazepam-binding inhibitor (DBI)-processing products, acting at the mitochondrial DBI receptor, mediate adrenocorticotropic hormone-induced steroidogenesis in rat adrenal gland.

Regulation of sterol carrier protein 2 (SCP2) gene expression in rat peritoneal macrophages during foam cell formation. A key role for free cholesterol content.

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