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)

Fatty acid oxidation in brain microvessels decreased greatly when persistent hypertension developed in spontaneously hypertensive rats (SHR). Treatment of SHR with pantethine [D-bis-(N-pantothenyl-beta-aminoethyl) disulfide] in vivo for 4 weeks restored their fatty acid oxidation activity to the control level. The mechanism of the activating effect of pantethine on fatty acid oxidation was investigated in brain microvessels. Pantethine and its metabolites (pantetheine and 4'-phosphopantetheine) activated three steps of fatty acid oxidation, i.e., acyl-CoA synthetase, carnitine acyltransferase and intramitochondrial oxidation. The relation between changes in fatty acid oxidation activities and injuries of brain microvessels and the protective effect of pantethine against such injuries is discussed.
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PMID:Effect of pantethine on fatty acid oxidation in microvessels of rat brain. 663 48

The properties and characteristics of acyl-CoA synthetase from the arterial wall of rats were investigated. The enzyme is located mainly in the microsomes. Its activity was found to be maximal at pH 7.0-8.0, and to be completely dependent on ATP, CoASH and Mg2+. The Km values for these substances were the same as those of the enzyme in liver. The activity was affected by serum, divalent cations, albumin, lipoproteins and phospholipids. In rats, the activity was decreased in various pathological conditions, such as tocopherol deficiency, hypertension and diabetes mellitus and was increased in hypercholesterolemia. The physiological significance of this enzyme in free fatty acid metabolism is discussed on the basis of these results.
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PMID:Studies on acyl-CoA synthetase in rat arterial wall. 745 88

The XL-I form of xenobiotic-metabolizing medium-chain fatty acid:CoA ligase was purified to apparent homogeneity from bovine liver mitochondria. The procedure gave rise to a 435-fold increase in specific activity, with a yield of 12%. The enzyme eluted from a gel filtration column as a single peak with an apparent molecular weight of ca. 55,000. It ran as a single band on SDS-polyacrylamide gel electrophoresis (SDS-PAGE) which had an apparent molecular weight of 62 kDa. N-Terminal sequence analysis of the enzyme gave no sequence, which indicates a blocked N-terminus. To obtain sequence data, the enzyme was cleaved at methionine residues using CNBr. The resulting peptides were separated by SDS-PAGE. The cleavage pattern revealed two large peptides with molecular weights of ca. 10,000 and 12,000, plus several smaller peptides of lesser intensity. The 10 kDa and 12 kDa peptides were electroblotted onto Trans-Blot, and then sequenced directly from the blot. The N-terminal sequences of these two peptides are presented. When compared with known sequences it was discovered that these two peptides both have high homology with regions of the SA essential hypertension protein. This suggests a role for a carboxylic acid:CoA ligase in the control of high blood pressure.
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PMID:Purification and partial sequencing of the XL-I form of xenobiotic-metabolizing medium chain fatty acid:CoA ligase from bovine liver mitochondria, and its homology with the essential hypertension protein. 921 7

We recently reported that genetic polymorphisms of SAH, an acyl-CoA synthetase for fatty acids, might contribute to multiple risk factors, especially hypertriglyceridemia. There are at least 4 members in this SAH gene family, SAH, MACS1, MACS2, and MACS3, and these 4 members are clustered in human Ch16p12. It is possible either that the previously observed associations were due to linkage disequilibrium with truly important polymorphisms in other members of the SAH gene family or that other polymorphisms in this gene family may also influence multiple risk factors. Thus, we performed association studies between genetic polymorphisms in this SAH region and multiple risk factors, using a large cohort representing the general population in Japan. The L513S polymorphism in MACS2 was shown to significantly influence the triglyceride level and the waist-to-hip ratio. The previously observed associations between an SAH polymorphism and the waist-to-hip ratio appear to be due to linkage disequilibrium with the L513S polymorphism. Haplotype analysis indicated that a haplotype defined by the I/D polymorphism of SAH and the L513S polymorphism in MACS2 was highly significantly associated with the triglyceride level. This study confirmed the importance of this chromosomal region in the pathogenesis of hypertriglyceridemia and visceral obesity.
Hypertension 2003 May
PMID:An acyl-CoA synthetase gene family in chromosome 16p12 may contribute to multiple risk factors. 1265 5

Although the SA gene was first identified as a putative candidate gene to understand the molecular basis of hypertension in rat and humans, the concept has not been supported in recently generated SA-null mice. We had first identified the mouse SA gene on the basis of its strong androgenic regulation in mouse kidney and further characterized its genomic organization, transcription start site and chromosomal location. Northern blot, RT-PCR and in situ hybridization assays determined mouse strain, tissue distribution, sex-hormone dependence and cell expression of the SA) mRNA. Kidney and liver constitute the main expression sites of the SA gene; in particular it is expressed in epithelial proximal tubule cells in the presence of androgens. This androgen-dependent expression is abrogated when estrogens are also present. By using the sensitive RT-PCR technique, minor SA expression sites, corresponding to testes, stomach, heart and lung, have also appeared. Like in kidney, expression of the SA gene in heart and lung is androgen-dependent. Production of rabbit antibodies against SA-synthetic peptides identified the SA protein, a moiety of unknown function, which has been defined as a member of the acyl-CoA synthetase family. We have determined that the SA protein follows the same distribution and regulation as its corresponding mRNA. Transient transfection assays followed by confocal microscopy identified the mitochondria of proximal tubule-derived PCT3 cells as the subcellular location of the SA protein. Different transcriptional units produced by splicing events, occurring before the translation initiation site, have been identified from mouse kidney. This work provides the basis to further understand the molecular mechanisms that control the sex-steroid-dependent expression of the SA gene in mouse kidney, heart and lung, where SA is also expressed in an androgen-dependent manner.
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PMID:Sex steroid regulation and identification of different transcription units of the SA gene in mouse kidney. 1552 78