Disease relevance of Sec14l2

• Moreover, SPF was not detectable in most of the cell lines tested, including HepG2 and McARH7777 hepatomas [1].
• To determine if SPF2 was also able to stimulate squalene monooxygenase activity, we have cloned, expressed, and purified the protein following heterologous expression in Escherichia coli [2].
• Because the growth plates of SPF and SAL rats were substantially not different, modifications observed in the NX rats cannot be attributed to the nutritional deficit associated with renal failure [3].
• To characterize the modifications of growth plate in individuals with growth impairment secondary to chronic renal failure, young rats were made uremic by subtotal nephrectomy (NX) and, after 14 d, their tibial growth plates were studied and compared with those of sham-operated rats fed ad libitum (SAL) or pair-fed with NX (SPF) [3].
• In accordance with the elongation of the hypertrophic stratum in uremia, the distance (X+/-SEM, microm) between the extracellular ChM-I signal and the metaphyseal end of growth cartilage was higher (P < 0.003) in UREM (236 +/- 40) and UREM-GH (297 +/- 17) than in SAL (92 +/- 7) and SPF (113 +/- 6) [4].

Psychiatry related information on Sec14l2

• The results demonstrated that neurons in the BNSTpm, PD, MEApd, and SPFp that project to the MPN were activated following copulation [5].

High impact information on Sec14l2

• Collagenase digestion of tissue slices from perfused, lavaged SPF rat lung released approximately 10(8) viable mononuclear cells per gram tissue, which comprised 35% T lymphocytes and up to 26% macrophages [6].
• Supernatant protein factor, which stimulates the conversion of squalene to lanosterol, is a cytosolic squalene transfer protein and enhances cholesterol biosynthesis [1].
• In 1957, Bloch and colleagues identified a factor from rat liver cytosol termed "supernatant protein factor (SPF)," which promotes the squalene epoxidation catalyzed by rat liver microsomes with oxygen, NADPH, FAD, and phospholipid [Tchen, T. T. & Bloch, K. (1957) J. Biol. Chem. 226, 921-930] [1].
• Transfection of SPF cDNA in McARH7777 significantly stimulated de novo cholesterol biosynthesis [1].
• SPF is expressed significantly in isolated hepatocytes, but the expression level was markedly decreased after 48 h of in vitro culture [1].

Chemical compound and disease context of Sec14l2

• Supernatant protein factor requires phosphorylation and interaction with Golgi to stimulate cholesterol synthesis in hepatoma cells [7].
• Evaluation of 2,3-oxidosqualene synthesis from [(14)C]mevalonate demonstrated that SPF also stimulated squalene monooxygenase (1.3-fold) in hepatoma cells [8].
• Substitution of [(14)C]mevalonate for [(14)C]acetate in McARH7777 hepatoma cells expressing SPF reduced the 1.8-fold increase in cholesterol synthesis by half, suggesting that SPF acted on or prior to mevalonate synthesis [8].
• Addition of dibutyryl-cAMP, a PKA activator, to hepatoma cells expressing SPF increased cholesterol synthesis by 62%, whereas addition of a cell-permeable PKA inhibitor blocked the SPF-mediated increase in cholesterol synthesis [7].
• RESULTS: Renal failure was confirmed by concentrations (X +/- SEM) of serum urea nitrogen (mmol/L) and creatinine (micromol/L) in UREM (20 +/- 1 and 89.4 +/- 4.5) and UREM-GH (16 +/- 1 and 91.4 +/- 6.9) that were much higher (P < 0.001) than those of sham animals (SAL, 3 +/- 0 and 26.5 +/- 2.2; SPF, 4 +/- 0 and 26.5 +/- 2.1) [9].

Biological context of Sec14l2

• Evidence is presented that the process of supernatant protein factor-mediated squalene transfer does not involve membrane fusion and proceeds also in the reverse direction [10].
• This SPF effect on enzyme kinetics indicates that SPF facilitates the otherwise rate-limiting access of squalene to the epoxidse site [11].
• The present study also investigated the functional association of the separate subdivisions of SPFp for male and female rat sexual behavior [12].
• 1. The aim of this study was to investigate the effect of the Na+/K+-ATPase on the membrane potential of peritoneal mast cells isolated from male Sprague-Dawley SPF-rats [13].
• Other SPF-derived strains had a similarly low susceptibility, thus pointing to an important external factor influencing the induction of autoimmunity by this procedure [14].

Anatomical context of Sec14l2

• SPF mRNA is expressed abundantly in the liver and small intestine, both of which are important sites of cholesterol biosynthesis [1].
• Digestion of intact microsomes with trypsin had no effect on the SPF-stimulated cyclase activity [15].
• The response of microsomal squalene epoxide-lanosterol cyclase to SPF was abolished by pretreatment of the membranes with phospholipase A2 or by low concentrations of deoxycholate, indicating that an intact membrane system is required [15].
• Growth plate height (mean +/- SD) was much greater (P<0.05) in NX (868.4+/-85.4 microm) than SAL (570.1+/-93.5 microm) and SPF (551.9+/-99.7 microm) rats as a result of a higher (P<0.05) hypertrophic zone (661.0+/-89.7 versus 362.8+/-71.6 and 353.0+/-93.9 microm, respectively) [3].
• In this zone, chondrocytes of NX animals were significantly (P<0.05) smaller (12080.4+/-1158.3 microm3) and shorter (34.1+/-2.5 microm) than those of SAL (16302.8+/-1483.4 microm3 and 37.8+/-2.0 microm) and SPF (14465.8+/-1521.0 microm3 and 36.3+/-1.8 microm) [3].

Associations of Sec14l2 with chemical compounds

• These results indicate that SPF2 activity is modulated by guanine nucleotides and alpha-tocopherol, as well as by phosphorylation [2].
• To confirm a role for PKA in the regulation of SPF, substitution of alanine for serine-289 (a putative PKA recognition site) blocked the stimulation of cholesterol synthesis by SPF [7].
• Phospholipid, specifically phosphatidylglycerol or phosphatidylethanolamine, is required for maximal stimulation of the cyclase by purified SPF [15].
• SPF also significantly enhances the formation of lanosterol from squalene-2,3-oxide already bound to microsomes [15].
• An amino acid analysis of SPF is presented, and the properties of SPF and of the various soluble protein activators of microsomal sterol biosynthesis described by other laboratories are compared [16].

Regulatory relationships of Sec14l2

• A soluble protein termed "supernatant protein factor" (SPF) that stimulates microsomal squalene epoxidase has been isolated in this laboratory (Ferguson, J.B., and Bloch, K. (1977) J. Biol. Chem. 252, 5381-5385) [15].

Other interactions of Sec14l2

• Regulation of rat liver microsomal squalene epoxidase: inactivation of the supernatant protein factor by nucleotides [17].

Analytical, diagnostic and therapeutic context of Sec14l2

• The present studies demonstrate that the ability of SPF to stimulate cholesterol synthesis in cell culture is also modulated by phosphorylation [7].
• By combining stereological and in situ hybridization techniques, we examined the expression patterns of types II and X collagens and collagenase-3 in tibial growth plates of rats made uremic by subtotal nephrectomy (NX) in comparison with those of sham-operated rats fed ad libitum (SAL) and sham-operated rats pair-fed with NX (SPF) [18].
• Using in situ hybridization histochemistry, we compared messenger RNA (mRNA) levels for the hypothalamic neurohormones GH-releasing hormone (GHRH) and somatostatin (SRIH) in three groups: rats with CRI induced by 5/6 nephrectomy (NPX, N = 4); sham-operated, ad libitum fed rats (SAL, N = 5); and sham-operated, pair-fed rats (SPF, N = 5) [19].
• METHODS: Growth cartilage ChM-I expression was investigated by immunohistochemistry, in situ hybridization, and reverse transcription-polymerase chain reaction (RT-PCR) in growth-retarded young uremic rats (UREM), control rats, fed ad libitum (SAL) or pair-fed with the UREM group (SPF), and uremic rats treated with growth hormone (UREM-GH) [4].
• 2. Plasma exudation induced by intrapleural injection of bradykinin (BK, 3 nmol per rat) into male SD strain rats (SPF, 8 weeks old) were significantly inhibited by oral administration of novel B2 receptor antagonist FR173657 (3-30 mg kg-1, 1 h before BK injection) in a dose-dependent manner, whereas that induced by histamine was not [20].

References