Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of an aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA), which blocks oestrogen formation, have been studied in female MRL/MP-lpr/lpr mice which are a model of SLE. At 11.5 weeks, mice were implanted subcutaneously either with empty Silastic implants or with implants containing 25 mg 4-OHA. At 15 weeks, they were sacrificed by decapitation and liver, thymus, kidneys and uterus taken for wet weight, histology and measurement of cytosolic and nuclear oestrogen receptors. Thymus weights were significantly lower in 4-OHA-treated mice although uterus weights were similar in both groups. Also, whereas thymuses from control-treated mice were packed with plasma cells with abundant cytoplasm, those from 4-OHA-treated mice contained T cells with large nuclei. Relative oestrogen receptor abundances were: uterus > liver > thymus, although cytosolic receptors could not be detected in thymus cytosols of MRL mice unless they were treated with the aromatase inhibitor. In kidney, there was histological evidence that inflammation was limited to mesangium in 4-OHA-treated mice. These results support the hypothesis that oestrogens may be involved in the aetiology of murine SLE and provide data suggesting that substances which block oestrogen production in vivo may be useful to treat certain forms of SLE.
Lupus 1993 Aug
PMID:Effects of an aromatase inhibitor on thymus and kidney and on oestrogen receptors in female MRL/MP-lpr/lpr mice. 826 69

Soy isoflavones supplements, which are phyto-oestrogens widely used as alternatives to alleviate menopausal syndromes or prevent chronic diseases, may exert oestrogenic and anti-oestrogenic activities. This study aimed to investigate the effects of soy isoflavones supplement on oestrogen-related autoimmune disease, such as systemic lupus erythematosus, using autoimmune-prone female MRL-lpr/lpr mice. Eighty mice of 8 weeks were divided into five groups: 0 (Control), 2 (Isf 2), 10 (Isf 10) and 20 (Isf 20) mg/kg BW/day Phyto Soya isoflavones or 0.375 mg/kg BW/day tamoxifen (TAM) as the positive control, by tube-feeding. Some mice were killed at age 15 weeks for cellular cytokine secretion. The data suggested that the Isf 20 and TAM groups had higher weight gain and survival compared with the control group. At age 22 weeks, the Isf 20 group still had 75% survival comparable to mice treated with TAM. At age 14 weeks, the TAM group showed significantly lower serum anti-double-stranded (ds) DNA IgG and anti-cardiolipin IgG. The mice in the Isf 10 and Isf 20 groups also had lower anti-dsDNA IgG and anti-cardiolipin IgG. The interferon (IFN)-gamma secretion from mitogen-stimulated T cells in the Isf 20 and TAM groups were significantly lower than those of control mice. Furthermore, the oestrogenic activity of the methanol extracts of soy isoflavones for oestrogen receptor (ER)beta, but not ERalpha, significantly increased, suggesting that soy isoflavones have a selective modulation of ER activation. Thus, soy isoflavone supplementation did not aggravate murine lupus, but apparently ameliorated the disease.
Lupus 2008 Sep
PMID:Soy isoflavones supplementation alleviates disease severity in autoimmune-prone MRL-lpr/lpr mice. 1875 63

Arylamine N-acetyltransferases (NATs) catalyse the N-acetylation of arylamines, arylhydroxylamines and arylhydrazines with the acetyl group being transferred from acetylCoenzyme A. As a result of many recent advances in NAT research there have been many recent reviews and the present paper gives a flavour of the excitement in the field. The NATs, which are cytosolic, were early examples of pharmacogenetic variation. Polymorphism in isoniazid inactivation resulting in slow acetylation was subsequently found to be due to SNPs in the gene encoding the human isoenzyme NAT2. There are two polymorphic genes (NAT1 and NAT2) encoded with a third pseudogene (NATP) at human 8p21.3. The gene structure of NAT1 and NAT2, with a single (NAT2) or multiple (NAT1) distant non-coding exons showing tissue specific splicing, opens possibilities for effects of polymorphisms outside the single coding exon. In humans, the substrate specificities of NAT1 and NAT2 are overlapping but distinct. The NAT2 isoenzyme, predominantly in liver and gut, acetylates sulphamethazine and arylhydrazine compounds. Slow acetylators are at increased risk of toxicity, e.g. isoniazid induced neurotoxicity and hydralazine-induced lupus. The human NAT1 isoenzyme is also polymorphic. It is expressed in many tissues, particularly in oestrogen receptor positive breast cancers. Human NAT1 has an endogenous role in acetylation of a folate catabolite with in vivo evidence from transgenic mice lacking the equivalent gene. For nomenclature see http://louisville.edu/medschool/pharmacology/NAT.html, the website maintained by David Hein. NAT homologues have been identified by bioinformatics analyses in zebrafish and these sequences are described, although the proteins have not yet been characterized. The first NAT crystallographic structure from Salmonella typhimurium identified the mechanism of acetyl transfer via a catalytic triad of Cys, His and Asp residues each essential for activity in all NATs. NATs from mycobacteria aided in identifying the substrate binding site and the acetylCoA binding pocket. Studies on the eukaryotic enzymes by NMR and crystallography have facilitated understanding substrate specificities of human NAT1 (5-aminosalicylate and p-aminobenzoic acid) and human NAT2 (sulphamethazine). The effect of "slow acetylator" SNPs in the coding region predominantly act through creating unstable protein that aggregates intracellularly prior to ubiquitination and degradation.
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PMID:Arylamine N-acetyltransferases: structural and functional implications of polymorphisms. 1885 12