Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kinetic investigations on the hepatocellular uptake of certain peptide-mimicking drugs revealed that in most cases carrier-mediated mechanisms are responsible for their rapid extraction from portal blood. The driving forces for uptake, however, are unknown. Uptake is not dependent on the presence of sodium ions. The membrane potential or other energy sources may drive their uphill transport. Efforts to isolate the transport proteins involved in hepatocellular uptake using the Xenopus laevis oocyte system failed due to high unspecific binding of the peptides. Intracellular cytosolic and membrane-associated binding proteins, however, were isolated and sequenced. Uptake of certain of the drugs investigated is related to the uptake of bile acids. The recently cloned bile acid transporters ntcp and oatp are not the related transport systems. The carrier protein for these peptide-mimicking drugs has yet to be cloned. At the canalicular pole of the cell, excretion of two linear renin-inhibitors EMD 51,921 and CGP 38,560 is due to ATP-dependent transport mechanisms. MDR gene products seem to be involved in the elimination of the renin-inhibitor CGP 38,560, whereas the endogenous ATP-dependent transport system for the renin-inhibitor EMD 51,921 has not been identified.
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PMID:Hepatobiliary elimination of certain peptide-mimicking drugs: linear hydrophobic and hydrophilic renin-inhibitors and hydrophobic cyclopeptides. 892 69

The S+S-Antilles transgenic mouse used in this study has renal defects similar to those seen in sickle cell anemia patients: congested glomeruli, medullary fibrosis, renal enlargement, vasoocclusion, and a urine concentrating defect. We used gene expression microarrays to identify genes highly up-regulated in the kidneys of these mice and validated their expression by real-time PCR. Kidney hypoxia, as demonstrated by the presence of deoxyhemoglobin, was detected by blood oxygen dependent magnetic resonance imaging (BOLD-MRI). Some of the up-regulated genes included cytochrome P450 4a14, glutathione-S-transferase alpha-1, mitochondrial hydroxymethylglutaryl CoA synthase, cytokine inducible SH-2 containing protein, retinol dehydrogenase type III, arginase II, glycolate oxidase, Na/K ATPase, renin-1, and alkaline phosphatase 2. An increase in enzyme activity was also demonstrated for one of the up-regulated genes (arginase II). These genes can be integrated into several different pathophysiological processes: a hypoxia cascade, a replacement cascade, or an ameliorating cascade, one or all of which may explain the phenotype of this disease. We conclude that microarray technology is a powerful tool to identify genes involved in renal disease in sickle cell anemia and that the identification of various metabolic pathways may open new avenues for therapeutic interventions.
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PMID:Differential gene expression in the kidney of sickle cell transgenic mice: upregulated genes. 1463 54

The genes of the renin--angiotensin system (RAS) play an important role in the regulation of pulmonary vascular tone. Although studies on individual genes polymorphisms have reported association with high-altitude pulmonary oedema (HAPE), studies on multiple genes or epistasis are lacking. We therefore investigated the association of the RAS polymorphisms with HAPE. In a case-control design, we screened 163 HAPE-resistant/controls (HAPE-r) and 160 HAPEpatients (HAPE-p) of Indian origin for eight polymorphisms of four RAS genes, ACE, AGT, AGTR1 and AGTR2. Significant difference in genotype and allele frequencies of the ACE I/D and AGT M235T polymorphisms was observed between HAPE-p and HAPE-r (p < 0.05). In three-locus haplotype analysis of AGT the haplotype GTM was significantly higher in HAPE-p (29%) and haplotype GTT in HAPE-r (27%) after Bonferroni correction (p < 0.006). The differences were insignificant for polymorphisms from AGTR1 and AGTR2. The MDR (multifactor dimensional reduction) approach for gene--gene interaction depicted individual polymorphism M235T as the best disease predicting model (cross validation consistency, CVC = 10/10). We found a significant association of D allele of ACE and M allele of AGT with HAPE. The findings are supported at the haplotypic level as well as through nested genetic interaction between the RAS gene polymorphisms using the MDR approach.
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PMID:Polymorphisms of renin--angiotensin system genes as a risk factor for high-altitude pulmonary oedema. 2139 62