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)

Glucocorticoid (GC) excess (Cushing's syndrome) is associated with hypertension in at least 70% of patients (in our series 89/130), independently of the subtype (pituitary or adrenal) and the duration, but not of the age of the patients. Cardiovascular damage is quite frequent in hypertensives, but is sometimes also present in normotensives. The mortality of patients with Cushing's syndrome is four times that of the general population when matched for age and sex, and much of this excess mortality is caused by cardiovascular disease. Hypertension remits in most of the patients after successful treatment, but may persist in some. Hypertension also occurs in 20% of patients treated with GC orally. The type of hypertension is independent of salt uptake, can not be controlled by spironolactone but is inhibited by a GC antagonist such as RU486. Experimentally-induced hypertension with oral cortisol (F) is associated with a rise in cardiac output, a fall in calculated total peripheral resistance, an increased forearm vascular responsiveness to exogenous norepinephrine, but no change in overall sympathetic tone, or in norepinephrine reuptake. The increased pressor responsiveness is probably due to local postsynaptic effector mechanisms in the resistance vessels, which could be important in phasic increases in neuronally mediated constrictor responses. Both in patients with Cushing's syndrome and in those on chronic GC treatment, the circadian blood pressure variations are absent or reversed. This may contribute to the deleterious effects of the GC excess on blood vessels. The vascular effects of the GC may be mediated by the activation of specific cardiovascular receptors, by modulating vascular transport systems, or by altered catecholamine or prostaglandin metabolism. GC may also act as mineralocorticoids (MC): in fact type 1 MC receptors are unable, in vitro, to distinguish between aldosterone and cortisol. The specificity-conferring mechanism of typical target organs for MC (e.g. kidney)--is thought to be due to the action of local 11-beta-hydroxysteroid dehydrogenase, which converts F to biologically inactive cortisone (E). When the activity of the enzyme is impaired (syndrome of apparent MC excess, liquorice or carbenoxolone administration), F acts as a MC and MC-hypertension with hypokalemia occurs.(ABSTRACT TRUNCATED AT 400 WORDS)
J Steroid Biochem Mol Biol 1992 Oct
PMID:Glucocorticoid-dependent hypertension. 139 Feb 89

Familial hypoalphalipoproteinemias (HA) are a heterogenous group of disorders characterized by various degrees of HDL deficiency. Differential diagnosis involves clinical and biochemical evaluation after intervention designed to correct known secondary causes of low HDL. Two specific HAs are discussed in this report: 1. primary isolated HA (PIHA) is a poorly characterized entity with an apparent autosomal dominant transmission and distinct abnormalities in the structure and function of HDL. 2. Lecithin: cholesterol acyltransferase (LCAT) deficiency syndromes are caused by a number of different genetic defects that lead to at least two distinct clinical presentations i.e. familial LCAT deficiency and fish eye disease. PIHA is an example of a genetic disorder whose diagnosis would greatly be improved by the availability of molecular diagnostic tests. Conversely, the effect of the genetic heterogeneity of LCAT deficiency syndromes on diagnosis is best overcome by utilizing existing biochemical measurement of LCAT activity and the plasma cholesterol esterification rate.
Mol Cell Biochem 1992 Aug 18
PMID:Analysis of familial hypoalphalipoproteinemia syndromes. 151 5

The increase of urinary albumin excretion has a predictive value for cardiovascular disease in insulin-dependent and non insulin-dependent diabetics. To study the relationship between urinary albumin excretion and serum lipids, 380 non insulin-dependent diabetics, 40 to 75 yr old, with urinary albumin excretion from 0 to 200 mg/l, and normal serum creatinine (less than 150 mumol/l), were surveyed. Urinary albumin excretion, was related positively to age (r2 = 0.014; p = 0.02), to systolic blood pressure (r2 = 0.073, p = 0.0001) and diastolic blood pressure (r2 = 0.052, p = 0.0001); a negative correlation existed with HDL-cholesterol (r2 = 0.043, p = 0.0001) and Apoprotein A1 (r2 = 0.044, p = 0.0001). A stepwise regression analysis was performed and resulted in three independently contributing variables related to urinary albumin excretion: First systolic blood pressure (F = 36), second Apoprotein A1 (F 24), third hemoglobin A1C (F = 6). The presence of hypertension or insulin therapy did not modify these findings. In conclusion, serum lipid seems an important determinant of urinary albumin excretion in non insulin-dependent diabetics.
Mol Cell Biochem 1992 Feb 12
PMID:Serum lipids and urinary albumin excretion in non insulin-dependent diabetics. 162 84

Inhibition of 11-beta-hydroxysteroid dehydrogenase (11-beta-OHSD) in the kidney can cause excess mineralocorticoid effect and hypokalemia. To find out if gossypol, a potential oral contraceptive for men that has been associated with cases of hypokalemia, inhibits this enzyme, its effect on guinea pig kidney was studied. Working with microsomes from the kidney cortex, and using corticosterone as the substrate, racemic gossypol was found to be a competitive inhibitor of 11-beta-OHSD with a Ki of 67 +/- 5 microM. The (+) enantiomer was a little more potent than the (-) enantiomer. Microsomes from the kidneys of animals given gossypol for 2 weeks had lower enzyme activities than saline-treated animals. Microsomes from a strain of hairless guinea pigs had lower intrinsic enzyme activity than the normal animals. We conclude that there is genetic variation in the activity of this enzyme and that it can be inhibited by gossypol.
J Steroid Biochem Mol Biol 1991 Aug
PMID:Inhibitory effects of gossypol on corticosteroid 11-beta-hydroxysteroid dehydrogenase from guinea pig kidney: a possible mechanism for causing hypokalemia. 188 75

Low (LDL) and high (HDL) density lipoproteins stimulate prostacyclin (PGI2) synthesis in cultured rabbit and human aortic smooth muscle cells. In this respect, the efficacy of HDL exceeded that of LDL, HDL3 being the most effective. HDL3 obtained from hypoalphacholesterolemic patients' serum had a lesser stimulative effect on PGI2 synthesis as compared with HDL3 of normolipidemic subjects. Partially purified apoprotein A-1 stimulates the metabolism of 14C-arachidonic acid accompanied with enhanced formation of prostaglandins, especially 6-keto-PGII alpha. Within a 24 h incubation in the fetal calf serum-free medium, prostaglandins I2 and E1 (1 x 10(-7) M) reduce the intracellular cholesterol level in human aortic smooth muscle cells by 30%. Total HDL fraction as well as HDL3 and HDL2b applied in combination with prostaglandins have a synergistic effect resulting in a 50% fall in intracellular cholesterol. Hypothetically, the uptake of cholesterol by HDL may include the following stages: (1) HDL interacts with the cell and activates the intracellular PGI2 synthesis probably via apo A-1 modulatory action on arachidonic acid metabolism; (2) newly synthesized PGI2 activates cholesteryl ester hydrolase leading to the formation of free cholesterol; (3) HDL takes up free cholesterol.
J Mol Cell Cardiol 1989 May
PMID:Prostacyclin-mediated effect of high density lipoproteins as cellular cholesterol acceptors on aortic smooth muscle cells. 267 51

In the present study serum lipoproteins were investigated during cell proliferation induced by a potent mitogen, lead nitrate. A strong decrease in HDL2 and a concomitant increase in HDL3 were observed in lead-treated rats. The recovery of normal lipoprotein pattern took place together with the regression of hyperplastic process. Since a decrease in HDL also occurs under other conditions of cell growth, we hypothesize that a decrease in HDL, mainly in HDL2 subfraction, may represent a generalized phenomenon related to massive cell proliferation.
Exp Mol Pathol 1989 Oct
PMID:Variations of serum lipoproteins during cell proliferation induced by lead nitrate. 280 72

Further studies were carried out on purified mouse Leydig cells to determine why they lose their hormone responsiveness after several days in monolayer culture. The effects of cholera-toxin on cyclic AMP and testosterone production were examined. It was found that cyclic AMP production could still be maximally stimulated by cholera-toxin after 4 days in culture when response to luteinizing hormone (LH) has declined. Testosterone production was, however, not maintained. Because this decline in testosterone production may have been due to the lack of a suitable substrate after several days in culture, cells were cultured initially in the presence of exogenous pregnenolone and low-density lipoproteins (LDL). Both substances were found to enhance basal and LH-stimulated testosterone production and to extend responsiveness of the cells until at least day 4, but by day 7 response was lost. Cells were then cultured in the presence of rat and human LDL and HDL and in both cases LDL was found to enhance consistently testosterone production, but HDL was much less effective. Scanning and transmission electron micrographs showed that changes in cell shape occurred during culture, but indicated that the cells were not depleted of lipid droplets by the end of culture or after LH stimulation. It is concluded that the eventual decline in testosterone synthesis is not due to lack of substrate, although the addition of exogenous substrate does extend the period of responsiveness. Nor is it due to a decrease in adenylate cyclase activity. At least part of the lesion is caused by a decrease in the enzymes required for the conversion of pregnenolone to testosterone.
Mol Cell Endocrinol 1985 Mar
PMID:The functional activity of adult mouse Leydig cells in monolayer culture: effect of lipoproteins, pregnenolone and cholera-toxin. 298 65

The presence of specific receptors for apolipoprotein B (low-density lipoproteins) and apolipoprotein E (HDL-E) on Hep-G2 cells and human skin fibroblasts was studied by chemical methods and by electron microscopy using a differential gold labeling technique. Fibroblasts bound both types of lipoproteins to one and the same receptor (B/E receptor) as deduced from competition experiments with HDL-E and LDL. Labeled HDL-E, on the other hand, was only partially displaced by cold LDL but was completely displaced by unlabeled HDL-E. Scatchard analysis of lipoprotein binding to Hep-G2 cells revealed an approx 10 times higher binding affinity of apoE-containing lipoproteins as compared to apoB-containing ones. No differences between apoE- or apoB-containing lipoproteins with respect to the morphology of cell binding and intracellular processing were observed. The results are compatible with the concept that Hep-G2 cells possess two kinds of receptors, one specific for apoB- and apoE-containing lipoproteins (B/E receptor) and another specific for apoE only. From these studies we conclude that Hep-G2 cells may serve as a suitable model for studying the lipoprotein metabolism in the liver.
Exp Mol Pathol 1987 Jun
PMID:The existence of B/E and E receptors on Hep-G2 cells: a study using colloidal gold- and 125I-labeled lipoproteins. 303 69

From a group of 20 patas monkeys (Erythrocebus patas), four high and four low responders to dietary cholesterol were selected for this study. The monkeys were paired according to their responsiveness to cholesterol, and ovariectomies were carried out on one group of the matched pairs. For the study, the monkeys were fed a Prudent Diet (at 0.1 mg cholesterol/cal) for 5 months preceding the ovariectomy and for 7 months after the ovariectomy followed by a Rich Diet (at 0.4 mg cholesterol/cal) for 7 months. Serum cholesterol, apo B, and apo A-I concentrations and cholesterol distributions were determined. We observed that while the monkeys consumed the Prudent Diet, total serum cholesterol. HDL cholesterol, and apo A-I increased in the ovariectomized group, but not in the control group. When they began consuming the Rich Diet, total serum cholesterol, apo B, and apo A-I concentrations increased in all monkeys, but increased more in the ovariectomized monkeys. The effect of the loss of ovarian function on lipoprotein metabolism is accentuated when the monkeys are fed a Rich Diet designed to be similar to a saturated fat, cholesterol-rich diet consumed by human beings.
Exp Mol Pathol 1987 Aug
PMID:Effect of ovariectomy on response to dietary cholesterol in patas monkeys (Erythrocebus patas). 311 79

The changes of plasma lipoproteins which occur during the development of nephrotic syndrome induced in the rat were investigated by the administration of the antineoplastic drug adriamycin. Rats received a single intravenous injection of the drug (7.5 mg/Kg) and were sacrificed 5, 10, 15, 20, 25, and 30 days after treatment. By monitoring plasma and urine albumin, four stages in the development of nephrosis were identified: (1) a prenephrotic stage, (2) a mild nephrosis with moderate albuminuria and hypoalbuminemia; (3) a severe nephrosis with massive albuminuria and severe hypoalbuminemia; and (4) a recovery stage in which plasma albumin showed the tendency to increase. Apart from a mild elevation of plasma triacylglycerols and VLDL observed as early as Day 5, no changes in plasma cholesterol and in the other lipoprotein classes were observed at the stage of mild nephrosis (Day 10). However, as the disease became more severe (Day 15-25) there was a striking increase of HDL1 (1.050-1.090 g/ml) and, above all, of HDL2 (1.090-1.210 g/ml). VLDL and LDL also increased but at a later stage. The elevation of HDL1 and HDL2 was associated with an increase of apolipoprotein A-I in plasma (fourfold increase). Moreover, the relative content of this apolipoprotein in HDL1 and HDL2 increased as the disease progressed from mild to severe, so that in severely nephrotic rats HDL1 and HDL2 contained almost exclusively A-I and C apolipoproteins. HDL enriched in apolipoprotein A-I were also found in urine of severely nephrotic animals. Since these findings are similar to those previously described in nephrotic syndrome induced by puromycin aminonucleoside (Gherardi, E., and Calandra, S. (1982). Biochim. Biophys. Acta 710, 188.) the following conclusions can be drawn: (1) the key signs of nephrotic syndrome (albuminuria and hypoalbuminemia) precede the elevation of plasma lipoproteins; (2) the pattern of nephrotic hyperlipoproteinemia evolves as a function of the severity of the disease; (3) the accumulation of HDL enriched in apolipoprotein A-I represents an early and specific feature of nephrotic hyperlipoproteinemia in the rat.
Exp Mol Pathol 1983 Dec
PMID:Plasma and urine lipoproteins during the development of nephrotic syndrome induced in the rat by adriamycin. 641 89


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