Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the relationship between cardiac hypertrophy associated with hypertension, and the alterations in myocardial lipid metabolism, nicardipine (160 mg/kg/day), hydralazine (40 mg/kg/day), and enalapril (30 mg/kg/day) were administered to spontaneously hypertensive rats from 20 to 24 weeks of age. Drug administration significantly suppressed the increases in blood pressure and the ratio of left ventricular weight to body weight. A marked variation in the fatty acid binding capacities of the delipidated, dealbuminated heart cytosol obtained from these animals was observed in the 24-week-old rats (5.40 +/- 0.31 pmol/micrograms protein in non-treated rats; 4.73 +/- 0.34 pmol/mg protein in nicardipine-treated rats; 5.01 +/- 0.34 pmol/mg protein in hydralazine-treated rats; 4.61 +/- 0.26 pmol/mg protein in enalapril-treated rats) as compared to the 20-week-old non-treated rats (3.38 +/- 0.29 pmol/mg protein). The decrease in this capacity in the drug-treated groups closely correlated with the reduction of cardiac mass, suggesting that the factors governing regression may be closely related to those governing fatty acid binding capacity. It appears that fatty acid binding protein may play an important role in the hypertension-associated hypertrophic myocardium.
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PMID:Fatty acid binding protein of cardiac muscle in spontaneously hypertensive rats: effect of hypertrophy and its regression. 285 22

A protein from rat kidney was characterized that had several properties common to a multigene family of fatty acid binding proteins identified in other tissues. The putative kidney fatty acid binding protein (FABP) was purified from the soluble fraction of kidney homogenates using gel filtration and ion exchange chromatography. It was relatively abundant, had an apparent molecular mass of 15.5 kDa as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, bound equimolar amounts of oleic acid, and could be distinguished from other FABPs on the basis of size, amino acid composition, and tissue distribution. Polyclonal antibodies to kidney FABP were obtained and used to show that only kidney contained the 15.5-kDa protein, although the antibodies also recognized a slightly larger and less abundant protein in kidney that also was present in bladder. Rat kidney also contained heart FABP, and the properties of both FABPs in rat kidney were compared. The distribution of both proteins within the kidney differed, with kidney FABP being localized almost exclusively within the cortex, whereas heart FABP was found both in cortex and medulla. Kidney FABP was expressed developmentally after the neonatal period, whereas heart FABP was present in both neonatal and adult kidney at comparable amounts. Hypertension induced by mineralocorticoids or infusion of angiotensin II caused a marked suppression of kidney FABP expression, whereas amounts of heart FABP in kidney were unchanged. The studies showed that rat kidney contains at least two FABPs, and that these proteins are differentially regulated, suggesting that functional differences between the proteins may exist.
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PMID:Properties and differential regulation of two fatty acid binding proteins in the rat kidney. 317 Jun 9

The effect of hypertension on the expression of a fatty acid binding protein localized in the rat aorta was studied. The presence of rat heart fatty acid binding protein (hFABP) was documented in aortic tissue by using a cDNA probe and polyclonal antibodies. Hypertension was induced in groups of rats by implantation of deoxycorticosterone acetate in conjunction with 1% salt in the drinking water (deoxycorticosterone/salt). By the third week of this treatment a marked reduction (by a factor of 20) in the expression of hFABP mRNA in aorta was found, concomitant with a reduction in immunologically detectable protein, suggesting transcriptional regulation. This effect was tissue specific, since no change in the normal amounts of hFABP mRNA in heart, skeletal muscle, or kidney was found. This reduction in aortic hFABP mRNA was also found in mildly hypertensive uninephrectomized rats given salt but no deoxycorticosterone and in normotensive rats given deoxycorticosterone but no excess salt intake. A marked decrease in aortic hFABP mRNA also was observed in the Goldblatt two kidney-one clip hypertensive model, and administration of angiotensin II for 6 days by osmotic minipump also caused a reduction. These findings suggest that hFABP is under complex regulation in aortic tissue and is suppressed by arterial hypertension.
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PMID:Hypertension induces tissue-specific gene suppression of a fatty acid binding protein in rat aorta. 317 61

The level of renal fatty acid binding protein (FABP) was quantified by a specific radial immunodiffusion method using an antibody to cytosolic FABP in stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) at 5, 10, 20 and 40 weeks of age. Increased levels were found in the SHRSP medulla, but not in the WKY medulla. The increase occurred in the hypertension development period, reaching a peak at 20 weeks of age. This increase was confirmed by immunoblotting. There was no significant change of FABP in the cortex. To elucidate the mechanism responsible for these changes in the FABP level, three antihypertensive drugs (nicardipine, hydralazine and enalapril) were given to SHRSP at 20 weeks of age for a period of four weeks. Antihypertensive treatment significantly inhibited the development of hypertension and the increase in the medullary FABP level. The differential response of FABP in SHRSP and WKY suggests that this protein may play an important role in the cellular metabolism of fatty acids under the pathological condition of high blood pressure.
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PMID:Increased renal fatty acid binding protein in spontaneously hypertensive rats. 318 72

Fatty acid binding protein was purified from renal medulla, and its binding activity and fatty acid composition were determined in spontaneously hypertensive stroke-prone rats (SHRSP). Wistar-Kyoto rats (WKY) were used as controls. Fatty acid binding activity was higher in 5-week-old prehypertensive SHRSP than in control WKY (0.155 +/- 0.006 vs 0.030 +/- 0.001 mol palmitic acid/mol protein). However, in 40-week-old rats, the activity was decreased only in SHRSP with established hypertension (0.035 +/- 0.002 vs 0.028 +/- 0.003 mol palmitic acid/mol protein WKY). Fatty acid compositions were similar among 5-week-old and 40-week-old control WKY and 5-week-old SHRSP (palmitic acid, 24%; stearic acid, 14%; oleic acid, 30%; linoleic acid, 29%; arachidonic acid, 3%), although the total amount of bound long-chain fatty acids was decreased in 5-week-old SHRSP, explaining the high fatty acid binding activity in this preparation. Fatty acid binding protein from 40-week-old SHRSP had an elevated proportion of endogenous arachidonic acid, with other fatty acids being relatively reduced (palmitic acid, 8%; stearic acid, 2%; oleic acid, 4%; linoleic acid, 10%; arachidonic acid, 76%), indicating increased arachidonic acid transport in the cytosol. These results show that genetically hypertensive rats had an alteration in fatty acid transport mediated by fatty acid binding protein; this alteration may be involved in the pathogenesis of hypertension.
Hypertension 1987 Jul
PMID:Fatty acid binding protein in kidney of normotensive and genetically hypertensive rats. 359 73

Fatty acid binding protein was purified from renal medulla, and its binding activity and fatty acid composition were determined in spontaneously hypertensive stroke-prone rats. Wistar-Kyoto rats were used as controls. Fatty acid binding activity was higher in 5-week-old prehypertensive spontaneously hypertensive stroke-prone rats (0.155 +/- 0.006 mol palmitic acid/mol protein) as compared with control values in Wistar-Kyoto rats (0.030 +/- 0.001). However, in 40-week-old rats, the activity was decreased only in spontaneously hypertensive stroke-prone rats with established hypertension (0.035 +/- 0.002), and it did not decrease in Wistar-Kyoto rats (0.028 +/- 0.003). Fatty acid compositions were similar among 5 and 40-week-old control rats and 5-week-old hypertensive rats (palmitic acid 24%, stearic acid 14%, oleic acid 30%, linoleic acid 29%, arachidonic acid 3%), although the total amount of bound long-chain fatty acids was decreased in 5-week-old hypertensive rats, explaining the high fatty acid binding activity in this preparation. Fatty acid binding protein from 40-week-old hypertensive rats had an elevated proportion of endogenous arachidonic acid, with other fatty acids being relatively reduced (palmitic acid 8%, stearic acid 2%, oleic acid 4%, linoleic acid 10%, arachidonic acid 76%), indicating increased arachidonic acid transport in the cytosol. These results show that genetically hypertensive rats had an alteration in fatty acid transport mediated by fatty acid binding protein; this alteration may be involved in the pathogenesis of hypertension.
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PMID:[Studies on the function of fatty acid binding protein in hypertensive rat kidney]. 369 30

It is unknown how heme is distributed intracellularly from its site of synthesis in the mitochondria to other organelles. In previous work (Biochemistry 23, 3715, 1984) the transfer of heme from lipid bilayers to soluble proteins had been found to be independent of the recipient proteins' affinity for heme. Here, we investigated whether proteins are involved in the transfer of heme from biological membranes into aqueous media. We followed the release of 14C-labeled heme, from mitochondria preloaded with the heme, to BSA and found that only about 28%, of the heme was extracted on the first wash. After the third wash 35-50% of the heme that had been partitioned into the membranes was extracted. Fourth and fifth washes with BSA or a cytosolic heme-binding protein (HBP, also known as liver fatty acid binding protein) removed only insignificant amounts of 14C-labeled heme. Similarly, a large portion of the preloaded 14C-labeled heme could not be extracted from a variety of isolated membranes (inner and outer mitochondrial membranes, plasma membranes of liver cells, kidney cortex cells and erythrocyte membranes). By contrast, essentially all [14C]palmitate preloaded in biological membranes and all 14C-labeled heme preloaded in synthetic membranes was released to albumin (Biochemistry 23, 3715, 1984). These observations suggest that, in general, heme associates with membrane components which can be distinguished into two compartments. One compartment releases its heme spontaneously, while another compartment binds heme so tightly that a specific process has to be evoked for its release.
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PMID:Studies on the efflux of heme from biological membranes. 791 39

An alanine to threonine substitution at codon 54 of the fatty acid binding protein 2 (FABP2) gene has been associated with insulin resistance in Pima Indians and with obesity in aboriginal Canadians. We investigated whether this polymorphism contributes to obesity and insulin resistance in 258 Japanese subjects. Thirty-six subjects (13.9%) were homozygous for the Thr54 allele, 106 (41.1%) were heterozygous for the Ala54/Thr54 allele, and 116 (45.0%) were homozygous for the Ala54 allele. The frequency of the Thr54 allele was 0.34 and did not differ significantly between men and women. The incidence of non-insulin-dependent diabetes mellitus (NIDDM) was not different among the three genotypes. The variation at codon 54 of the FABP2 gene was not associated with obesity, hypertension, dyslipidemia, hyperuricemia, or hyperinsulinemia. These results suggest that the polymorphism at codon 54 of the FABP2 gene is not a major contributing factor to obesity and insulin resistance in Japanese subjects.
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PMID:Variation of the fatty acid binding protein 2 gene is not associated with obesity and insulin resistance in Japanese subjects. 1033 70

We studied by PCR-RFLP 6 polymorphisms in these 5 candidate genes: Ala54Thr in the fatty acid binding protein 2 gene (FABP2), A to G substitution in the uncoupling protein type 1 gene (UCP1), Asp905Tyr in the protein phosphatase type 1 gene (PP1G), Trp64Arg in the human beta 3 adrenergic receptor gene (beta 3AR) and 2 RFLP sites of the vitamin D receptor (VDR) gene (VDRTaq1 and VDRApa1). This study was conducted among 89 cases and 100 controls matched according to age, gender and absence of first degree family link (11 triplets with 2 controls for 1 case and 78 pairs with 1 control for 1 case). Cases and controls were taken among a sample of 429 individuals selected for the study of the prevalence of diabetes in this ethnic group from Guadeloupe. By conditional logistic regression analysis, there was a significant relation (p = 0.02) between the Ala54Thr FABP2 polymorphism and Type 2 DM. Multivariate analysis discriminate the FABP2 polymorphism (p = 0.10), a triglyceridemia over 2 g/l (p < 10(-3)) and high blood pressure (p = 10(-2)) as variables associated with Type 2 DM in this population. These findings suggest that FABP2 does not represent a major gene for Type 2 DM in this migrant Indian population living in Guadeloupe, but seems to be related to the metabolic insulin resistance syndrome.
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PMID:Type 2 diabetes mellitus: association study of five candidate genes in an Indian population of Guadeloupe, genetic contribution of FABP2 polymorphism. 1044 26

The metabolic syndrome is a cluster of metabolic and inflammatory abnormalities including obesity, insulin resistance, type 2 diabetes, hypertension, dyslipidemia, and atherosclerosis. The fatty acid binding proteins aP2 (fatty acid binding protein [FABP]-4) and mal1 (FABP5) are closely related and both are expressed in adipocytes. Previous studies in aP2-deficient mice have indicated a significant role for aP2 in obesity-related insulin resistance, type 2 diabetes, and atherosclerosis. However, the biological functions of mal1 are not known. Here, we report the generation of mice with targeted null mutations in the mal1 gene as well as transgenic mice overexpressing mal1 from the aP2 promoter/enhancer to address the role of this FABP in metabolic regulation in the presence or absence of obesity. To address the role of the second adipocyte FABP in metabolic regulation in the presence and deficiency of obesity, absence of mal1 resulted in increased systemic insulin sensitivity in two models of obesity and insulin resistance. Adipocytes isolated from mal1-deficient mice also exhibited enhanced insulin-stimulated glucose transport capacity. In contrast, mice expressing high levels of mal1 in adipose tissue display reduced systemic insulin sensitivity. Hence, our results demonstrate that mal1 modulates adipose tissue function and contributes to systemic glucose metabolism and constitutes a potential therapeutic target in insulin resistance.
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PMID:Role of the fatty acid binding protein mal1 in obesity and insulin resistance. 1254 Jun


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