Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Steroid metabolism was investigated in cultured human B-lymphoblastoid cells (B-LCL), and peripheral blood T and B cells. Gene expression was examined by reverse-transcription polymerase chain reaction amplification (RT-PCR). Appropriate sized transcripts were detected in both cultured and fresh peripheral lymphocytes for CYP11A, CYP17, HSD11L (11beta-hydroxysteroid dehydrogenase I), HSD17B1 (17beta-hydroxysteroid dehydrogenase type I) and SRD5A1 (5alpha-reductase I). B-LCL, but not T and B cells, expressed CYP11B. There was minimal expression of HSD3B1 and HSD3B2 (3beta-hydroxysteroid dehydrogenase I and II) in B-LCL and T cells. Transcripts for CYP19 and HSD11K were not detected. Corresponding enzymatic activity was detectable only for 17-hydroxysteroid dehydrogenase and 5alpha-reductase, respectively producing testosterone and 5alpha-dihydrotestosterone. Steroid identities were confirmed by gas chromatography/mass spectrometry (GC/MS). One metabolite thought to be deoxycorticosterone was identified by GC/MS as 6alpha-hydroxypregnanolone. It was concluded that sex hormone metabolism, including androgen synthesis, occurs in lymphocytes, and may modulate immune response.
Mol Cell Endocrinol 1998 Mar 16
PMID:Prominent sex steroid metabolism in human lymphocytes. 968 15

The large ethnic differences in prevalence of coronary artery disease between China and Europe may relate to both genetic and environmental differences. To assess possible genetic factors we have therefore studied the frequencies of disease-related variants of genes involved in lipid transport in 69 hypertriglyceridemic Chinese subjects and 74 healthy Chinese controls. The loci studied include lipoprotein lipase (Asp9Asn, Asn291Ser, Ser447Ter, and Thr361Thr); apolipoprotein A1 (restriction sites at MspI, XmnI, and PstI); and apolipoprotein (apo) CIII (G3175C). All these variants have been shown in previous literature publications to relate to either dyslipidemia and/or premature coronary heart disease in Caucasians. Two disease-related genetic variants in Europeans (Asp9Asn and Asn291Ser) were not found in the Chinese sample. The apo CIII G3175C variant was found more frequently in the upper tertile distributions for apolipoprotein CIII, apolipoprotein E, and plasma triglyceride/HDL ratios (P < 0.05). The rare allele of the apo AI MspI restriction site polymorphic variant was also found more frequently in the upper tertiles for apo CIII, apo E, and plasma triglyceride/HDL ratios (P < 0.04). Eleven of the most lipaemic Chinese subjects (with fasting plasma triglycerides >700 mg/dl) were analyzed for DNA sequence variation. One novel mutation was observed C1338A (which is a silent mutation at Thr361) and two others that are also found in European subjects (Ala261Thr and Ser447Ter). We conclude that genetic differences between Chinese and Europeans may have an effect on the prevalence of coronary artery risk factors involved in lipid transport, and further extended study is warranted.
Mol Genet Metab 1998 Jul
PMID:Common genetic variants of lipoprotein lipase and apolipoproteins AI-CIII that relate to coronary artery disease: a study in Chinese and European subjects. 971 26

This study evaluated the levels and the enzymatic characteristics of 11beta-hydroxysteroid dehydrogenase activity (11beta-HSD) of chorionic villi isolated from first trimester human placenta. The results demonstrated a predominant expression of the NAD-dependent dehydrogenase isoform (11beta-HSD2) over the NADP-dependent oxoreductase (11beta-HSD1). Thus, in tissue homogenates exogenous NAD increased the conversion of corticosterone to 11-dehydrocorticosterone of about 14-fold while NADP was ineffective. There was no conversion of 11-dehydrocorticosterone to corticosterone either with NADH or NADPH demonstrating the lack of reductase activity. In keeping with these results, RT-PCR analysis indicated a mRNA for 11beta-HSD2 in villous tissue while 11beta-HSD1 mRNA levels were undetectable. In addition, immunohistochemical staining localized the 11beta-HSD2 protein to syncytiotrophoblasts and cell columns of the chorionic villi. These results suggest roles for the trophoblast-associated 11beta-HSD2 oxidative activity in modulating the exposure of the embryo to active glucocorticoids in the early gestation and in regulating trophoblasts invasion of the uterine wall.
Mol Cell Endocrinol 1998 Jun 25
PMID:11Beta-hydroxysteroid dehydrogenase expression in first trimester human trophoblasts. 972 80

Physiological responses due to steroid hormones and retinoids are regulated by their cognate receptors and dehydrogenases. The origins of either regulatory mechanism are not fully understood. Here we examine the origins of the human 11beta-hydroxysteroid dehydrogenase-type 2, which regulates access of glucocorticoids to cells, and 17beta-hydroxysteroid dehydrogenase-type 2, which regulates access of androgens and estrogens to cells. Sequence comparisons trace their ancestry to homologs in Caenorhabditis elegans. These C. elegans proteins most closely resemble mammalian all-trans and 11-cis-retinol dehydrogenases. The similarity is sufficient -37% to 43% identity to suggest that one or more of the C. elegans homologs metabolizes a retinoid. Receptors for retinoids, but not for androgens, estrogens or glucocorticoids have been identified in C. elegans, suggesting that retinoid-mediated gene transcription is more ancient than that for adrenal and sex steroids. We propose that the hydroxysteroid dehydrogenase-type 2 mechanism for regulating the androgen, estrogen and glucocorticoid concentrations in mammals descended from that for regulating retinoid concentrations. Interestingly, E. coli contains a protein with strong sequence similarity to mammalian retinol dehydrogenases. Sequence comparisons and phylogenetic analysis indicate that the E. coli protein may be an example of horizontal transfer from a eukaryote ancestor.
J Steroid Biochem Mol Biol 1998 Sep
PMID:Evolution of mammalian 11beta- and 17beta-hydroxysteroid dehydrogenases-type 2 and retinol dehydrogenases from ancestors in Caenorhabditis elegans and evidence for horizontal transfer of a eukaryote dehydrogenase to E. coli. 974 41

3T3-L1 and human preadipocyte differentiation was significantly (P < 0.001) enhanced by HDL2, LDLII/III and LDLIV. The concentrations of lipoproteins required for maximal differentiation in human preadipocytes were not achieved over the concentration range 50-150 micrograms lipoprotein protein ml-1, whereas maximal differentiation in 3T3-L1 preadipocytes was achieved for all lipoprotein subfractions at approximately 75 micrograms lipoprotein ml-1, a level almost double that required for complete HDL and LDL fractions in 3T3-L1 cells. Despite the enhanced extent of differentiation caused by certain lipoprotein subfractions, the time needed for the conversion process was unaffected. GPDH activity development in both cell types was most pronounced in response to LDLIV, with HDL2 resulting in the lowest activity. In both cell types, the enhancement of differentiation was only evident when the cells were exposed to lipoproteins during the early stage of the program, i.e. before visible formation of lipid droplets.
Comp Biochem Physiol B Biochem Mol Biol 1998 Jul
PMID:The influence of plasma lipoprotein subfractions on 3T3-L1 and human preadipocyte differentiation in cell culture. 978 10

Chromium (Cr), an essential element, mainly affects saccharide (potentiated insulin action via interaction with insulin receptor on the cell surface) and lipid metabolism (inhibition of hydroxymethylglutaryl-CoA reductase with a hypolipidemic effect). The aim of the study was to describe Cr serum levels in different diseases (malignant, metabolic, renal) using an advanced analytical technique with correlation to other biochemical parameters. The concentration was measured using atomic absorption spectrometry with electrothermal atomization. The Cr levels were increased in hemodialysis patients-HD (3.67 +/- 0.35 micrograms/L) compared to controls-C (0.40 +/- 0.12 microgram/L), in significantly changed in diabetic patients-DM (0.29 +/- 0.08 microgram/L) and patients with lymphoproliferative disease-LP (0.24 +/- 0.07 microgram/L), and decreased in hyperlipidemic patients-HL (0.15 +/- 0.03 microgram/L). There were no differences in Cr concentration between DM treated by diet or peroral antidiabetic drugs; likewise hypolipidemic drugs in HL did not change the Cr concentration. The biochemical parameters-total protein, transferrin in LP group, glucose in DM group, total cholesterol, triacylglycerols, LDL-cholesterol, apolipoprotein B and A-I did not correlate with serum Cr concentration. However, the HDL-cholesterol concentration marginally significantly (p < 0.07) correlated with it. The role of Cr in humans has not yet been fully characterized. To prevent some complications in patients, it may be important to monitor the Cr levels. Chromium supplementation may be indicated in some diseases with no controversy concerning the importance of decreased serum and/or tissue levels and documented positive effects of Cr supplementation on the quality of life (e.g. hyperlipidemia).
Biochem Mol Biol Int 1998 Oct
PMID:Chromium levels in patients with internal diseases. 980 4

Non-insulin dependent diabetes mellitus (NIDDM) is associated with chronic hyperglycemia, which increases the risk of developing microvascular and macrovascular complications. Elevated triglyceride (TG) and VLDL cholesterol levels and low levels of HDL cholesterol have also been frequently reported in NIDDM patients. A diet high in complex carbohydrate and low in fat is typically recommended for management of NIDDM, however, this has recently been challenged by scientific reports of the benefits of dietary intakes high in monounsaturated fat. Thirty-two individuals with NIDDM were randomized to receive either Ensure with Fibre (30% fat) or a high monounsaturated fatty acid product, Glucerna (50% fat). These products were consumed for 28 days at > 80% of daily energy intake. Post-treatment, dietary compliance was verified by a higher plasma TG 18:1 n-9 (p < 0.001) in the Glucerna group and a higher plasma TG 18:2 n-6 (p < 0.001) in the Ensure with Fibre group. The postprandial rise in blood glucose levels, determined by fingerprick samples, was significantly lower (p < 0.01) in the Glucerna group. Trends of clinical interest were greater mean decreases in the Glucerna group compared to the Ensure with Fibre group in: fructosamine, 9.13 umol/L vs 0.14 umol/L; glucose, 1.61 mmol/L vs 0.63 mmol/L; and insulin, 46.0 pmol/L vs 12.6 pmol/L; respectively. However, overall, fasting plasma glucose, fructosamine, TG and cholesterol levels were not significantly different between groups. Thus, in these patients, the high monounsaturated fat diet and the standard diet were similar with regard to usual indicators of carbohydrate and lipid metabolism. A high monounsaturated fat diet appears to pose no risk to lipoprotein metabolism in NIDDM patients.
Mol Cell Biochem 1998 Nov
PMID:Effect of enteral nutritional products differing in carbohydrate and fat on indices of carbohydrate and lipid metabolism in patients with NIDDM. 982 14

Oxidized LDL is highly atherogenic as it stimulates macrophage cholesterol accumulation and foam cell formation, it is cytotoxic to cells of the arterial wall and it stimulates inflammatory and thrombotic processes. LDL oxidation can lead to its subsequent aggregation, which further increases cellular cholesterol accumulation. All major cells in the arterial wall including endothelial cells, smooth muscle cells and monocyte derived macrophages can oxidize LDL. Macrophage-mediated oxidation of LDL is probably a hallmark in early atherosclerosis, and it depends on the oxidative state of the LDL and that of the macrophages. The LDL oxidative state is elevated by increased ratio of poly/mono unsaturated fatty acids, and it is reduced by elevation of LDL-associated antioxidants such as vitamin E, beta-carotene, lycopene, and polyphenolic flavonoids. The macrophage oxidative state depends on the balance between cellular NADPH-oxidase and the glutathione system. LDL-associated polyphenolic flavonoids which inhibit its oxidation, can also reduce macrophage oxidative state, and subsequently the cell-mediated oxidation of LDL. Oxidation of the macrophage lipids, which occurs under oxidative stress, can lead to cell-mediated oxidation of LDL even in the absence of transition metal ions, and may be operable in vivo. Finally, elimination of Ox-LDL from extracellular spaces, after it was formed under excessive oxidative stress, can possibly be achieved by the hydrolytic action of HDL-associated paraoxonase on lipoprotein's lipid peroxides. The present review article summarizes the above issues with an emphasis on our own data.
Mol Cell Biochem 1998 Nov
PMID:LDL oxidation by arterial wall macrophages depends on the oxidative status in the lipoprotein and in the cells: role of prooxidants vs. antioxidants. 982 20

Severe hypertriglyceridemia was previously observed in mink. Affected animals had no detectable lipoprotein lipase activity, but normal amounts of lipoprotein lipase protein in post-heparin plasma. We have now cloned cDNA for lipoprotein lipase from normal mink and identified a single point mutation in the affected animals which most likely explains the deficiency of active lipase. The mutation is located in exon 6 and results in a Pro214Leu substitution. In heterozygote mink the levels of lipoprotein lipase activity and mass in post-heparin plasma were lower than in normal mink, but could not be used to identify carriers of the mutation. In some tissues (heart, muscle, kidney and lung), lipoprotein lipase activity was decreased to about 50%. In adipose tissue there seemed to be a mechanism to compensate for the mutation, resulting in increased mass and approximately the same activity of lipoprotein lipase as in animals not carrying the mutation. Mink had high lipoprotein lipase activity and mass in kidneys, although the levels of mRNA in kidney were many fold lower than in adipose tissue. Mink had very low levels of cholesteryl ester transfer protein activity in plasma. This may contribute to the high levels of HDL in this animal species.
Int J Mol Med 1998 Mar
PMID:A mutation in the lipoprotein lipase gene associated with hyperlipoproteinemia type I in mink: studies on lipid and lipase levels in heterozygotes. 985 58

Mineralocorticoids have been implicated in promoting fibrous tissue formation in various organs. In the present study, we sought to address the potential contribution of mineralocorticoids to fibrous tissue formation using a skin pouch model which has proved valuable for the analysis of inflammatory and wound healing responses. Skin pouches were induced in rats by administration of a phorbol ester, croton oil (0.5 ml of a 1% solution). After 2 weeks, rats were killed and intact pouch tissue collected. Pouch weights of control and aldosterone-treated (0.75 microg/h via osmotic minipump) rats were similar (3.33 +/- 0.44 g vs. 3.70 +/- 0.28 g respectively). However, pouch weights were reduced by more than 50% in spironolactone-treated (25 mg/day powdered in food) animals (1.62 +/- 0.22 g and 1.27 +/- 0.23 g respectively in aldosterone and spironolactone alone groups). To ascertain the effects of different treatments on collagen accumulation, hydroxyproline concentration was measured. Compared with controls, hydroxyproline concentration was significantly reduced following spironolactone treatment (17.1 +/- 0.08 vs. 7.5 +/- 2.0 microg/mg dry wt, respectively, p < 0.01). This response to spironolactone was negated by coadministration of aldosterone (hydroxyproline concentration was 18.6 +/- 2.1 microg/mg dry wt). Following bilateral adrenalectomy, spironolactone reduced pouch weight and hydroxyproline concentration, which was not the case for adrenalectomy alone. Two week aldosterone administration in uninephrectomized rats on high salt diet was deemed ineffective in modulating pouch development (pouch wet wts were 3.48 +/- 0.4 g vs. 3.00 +/- 0.19 g in controls and aldosterone-treated rats, respectively). Mineralocorticoid receptor expression in pouch tissue was demonstrated by RT/PCR. Furthermore, NADP+-dependent 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) activity was detected in pouch tissue, together with lower levels of NAD+-dependent 11beta-HSD2. Spironolactone (p < 0.05) significantly reduced 11beta-HSD1 activity compared with controls. Thus, fibrous tissue possesses requisite components of MC action, and antagonism of mineralocorticoid receptors by spironolactone attenuates its formation. Pouch formation is under the influence of circulating MC and, we would like to propose, is also mediated through corticosteroids generated de novo at the site of tissue repair.
Mol Cell Biochem 1998 Dec
PMID:Inhibition of tissue repair by spironolactone: role of mineralocorticoids in fibrous tissue formation. 987 53


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