Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously described a novel protein, derived from the 3B6 EBV B-cell line which apparently displayed IL-1 bioactivity. We report here that the protein previously characterized is not a new species of IL-1. Indeed, we have now been able to clone and express a cDNA which identifies this protein as human thioredoxin, an intracellular dithiol oxydo-reductase enzyme. Thioredoxin however, is not a lymphokine and in particular does not possess IL-1 activity. Our earlier data can be explained in the light of recent findings, reported herein, indicating that IL-1 alpha is produced by the 3B6 line as assessed by antibody inhibition studies and IL-1 alpha mRNA expression. Thus our original protein preparation actually contained traces of IL-1 alpha, which was responsible for the biologic activities and thioredoxin.
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PMID:Identification of interleukin 1 alpha produced by the 3B6 human EBV-B cell line. 254 Dec 84

Seborrhoea and acne are exclusively human diseases and sebaceous gland differentiation is species specific. Therefore, fundamental research on human sebaceous cell function and control requires human in vitro models. The human sebocyte culture model, introduced in 1989, has been used in several studies to elucidate sebaceous gland activity and its regulation at the cellular level. Cultured human sebocytes have been shown to preserve important sebocytic characteristics, although they undergo an incomplete terminal differentiation in vitro. In vitro synthesis of free fatty acids without bacterial involvement and marked interleukin 1 alpha expression at the mRNA and protein levels with no further induction by lipopolysaccharides lead to the assumption that human sebocytes may initiate acne lesions by an intrinsic mechanism. Androgens affected sebocyte activity in vitro in a manner dependent on the localization of the sebaceous glands. In vitro stimulation of sebocyte proliferation by androgens could be completely abolished by spironolactone. Cultured sebocytes strongly expressed type 1 5 alpha-reductase and metabolized testosterone to androstenedione, 5 alpha-androstanedione, 5 alpha-dihydrotestosterone, androsterone and 5 alpha-androstanediol, whereas the levels of 5 alpha-reductase activity were probably not feedback regulated. 4,7 beta-Dimethyl-4-aza-5 alpha-cholestan-3-one, a type 1 5 alpha-reductase inhibitor, induced an early, marked down-regulation of 5 alpha-reductase activity in human sebocytes in vitro, while hydrofinasteride, a type 2 inhibitor, required 10(3)-fold higher concentrations to induce similar effects. Stimulation of sebocyte proliferation by insulin, thyroid-stimulating hormone and hydrocortisone indicates that the hormonal control of the sebaceous gland could be a complex mechanism. Retinoids inhibited sebocyte proliferation in a dose-dependent manner and down-regulated lipid synthesis and sebocyte differentiation in vitro. Isotretinoin was the most potent compound. On the other hand, vitamin A was found essential for sebocyte activity and differentiation in vitro and could be partially substituted by synthetic retinoids. The inhibitory effect of isotretinoin on sebocyte proliferation was barely affected by the presence of vitamin A. The low persistent isotretinoin levels or, more likely, the considerably elevated tretinoin concentrations detected in human sebocytes after treatment with isotretinoin in vitro may be responsible for the inhibitory effect of this compound on sebocyte activity.
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PMID:The human sebocyte culture model provides new insights into development and management of seborrhoea and acne. 955 20

Linoleic acid deficiency, interleukin 1, retinoids and androgens have been implicated as causative factors in the follicular hyperkeratinization seen in acne. The goal of this study was to test the hypothesis that more androgens are produced in follicles of acne subjects compared to subjects without acne. Thirty-four subjects (males and females with and without acne) were studied. The activity of 5 alpha-reductase (5 alpha-R) and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) was determined in keratinocytes cultured from the infrainfundibulum and epidermis. Mean enzyme activities were slightly higher in the acne groups compared to the groups without acne, but differences were not statistically significant, perhaps due to limitations of this in vitro model. The activity of both 5 alpha-R and 17 beta-HSD was significantly greater in infrainfundibular keratinocytes compared to epidermal keratinocytes in all subject groups. 17 beta-HSD activity was 2.5- to 7-fold greater than the activity of 5 alpha-R in infrainfundibular keratinocytes. The regulation of 17 beta-HSD by endogenous factors may be important in determining the directional activity of 17 beta-HSD and hence the local concentration of testosterone within the infrainfundibulum. Additional studies of the effects of androgens on follicular keratinization are needed.
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PMID:Activity of 5-alpha-reductase and 17-beta-hydroxysteroid dehydrogenase in the infrainfundibulum of subjects with and without acne vulgaris. 955 22

Preterm delivery (PTD) appears to be a complex trait determined by both genetic and environmental factors. Few studies have examined genetic influence on PTD. The overall goal of our study is to examine major candidate genes of PTD and to test gene-environment interactions. Our study includes 500 preterm trios, including 500 preterm babies and their parents and 500 maternal age-matched term controls. We will perform the transmission/disequilibrium test (TDT) on candidate genes thought to be important in each of the four biological pathways of PTD: (1) decidual chorioamionotic inflammation: interleukin 1 (IL-1), IL-6, and tumour necrosis factor (TNF); (2) maternal and fetal stress: corticotropin-releasing hormone (CRH); (3) uteroplacental vascular lesions: methylenetereahydrofolate reductase (MTHFR); and (4) susceptibility to environmental toxins: GSTM1, GSTT1, CYP1A1, CYP2D6, CYP2E1, NAT2, NQO1, ALDH2, and EPHX. We will also perform standard case-control analyses on the 500 preterm cases and 500 term controls to examine gene-environment interactions. The major environmental, nutritional and social factors as well as clinical variables known or suspected to be associated with PTD will be used to test for gene-environment interactions. This study integrates epidemiological and clinical data as well as genetic markers along major pathogenic pathways of PTD. The findings from this study should improve our understanding of genetic influences on PTD and gene-environment interactions.
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PMID:Molecular epidemiology of preterm delivery: methodology and challenges. 1152 Apr 1

Oxidative stress response was determined in this study by enzyme-linked immunospot (ELISpot) assays for thioredoxin (Trx) and Trx reductase (TrxR). On exposure to oxidative stress, cells can launch a variety of defense mechanisms, including release of antioxidant proteins. The Trx system, consisting of Trx, TrxR, and NADPH, constitutes one of these cellular defense systems for maintenance of a healthy reduction-oxidation (redox) balance. Trx and TrxR are rapidly upregulated and released from monocytes, lymphocytes, and other normal and neoplastic cells on exposure. Secreted Trx and TrxR have proved to be eminent indicators of oxidative stress. Trx is a small, 12-kDa protein released through a leaderless pathway, whereas TrxR, which is a 116-kDa selenoprotein and required for regeneration of Trx, is secreted through the Golgi pathway. In this chapter we present a detailed laboratory bench protocol for enumeration of single cells secreting redox-active Trx and TrxR after oxidative stress exposure. Physiological stimuli (such as interferon gamma, lipopolysaccharide, interleukin 1, and CD23 ligation; and phorbol 12-myristate 13-acetate and ionophore) as well as UV light and hydrogen peroxide were used to generate oxidative stress, and some are presented in detail. The protocol includes a description of cell isolation, preparation, handling, and development of ELISpot plates, troubleshooting notes, presentation of results, statistical evaluation, and comments on alternative sources of materials and manufacturer Web addresses. We concluded that the ELISpot assay is a useful method for detection of single cells secreting the redox-active proteins Trx and TrxR after oxidative stress exposure.
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PMID:Enzyme-linked immunospot assay for detection of thioredoxin and thioredoxin reductase secretion from cells. 1207 96

Cytokines (IL-1, IL-6, IL-8, IL-11, TNF, IFN-gamma, and TGF-beta) and growth factors (EGF, bFGF, aFGF, and KGF) play an important role in modulation of hormone secretion by directly influencing specific enzyme steps of steroidogenesis in various endocrine cell types. For this tabular data collection, the following enzyme steps were considered: steroidogenic acute regulatory protein (StAR), side chain cleavage enzyme (P450scc), 3 beta-hydroxysteroid dehydrogenase, 17-alpha-hydroxylase/17,20-lyase (P450c17), 17-beta-hydroxysteroid-dehydrogenase, aromatase complex, 5-alpha-reductase, P450c21, DHEAS sulfatase, and DHEA sulfotransferase. This collection summarizes the current information on how the mentioned cytokines and growth factors influence particular enzyme steps.
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PMID:Influence of cytokines and growth factors on distinct steroidogenic enzymes in vitro: a short tabular data collection. 1211 70

Uptake of [14C]-azithromycin into THP-1 human monocytes was determined at pH 7.4, 6.8 or 5.5 over 4-log antibiotic concentrations for 24 h under a number of conditions. Stimulation of cells was with bacteria, latex beads, lipopolysaccharide (LPS), or zymogen A. Subcellular organelle disposition was determined after isolation by ultracentrifugation or sucrose gradients. Hydrolytic enzyme activities and mediators of intracellular inflammation (IL-1, IL-6, IL-8, and TNFalpha) were assessed. Azithromycin uptake into human THP-1 monocytes was initially linear achieving approximately 2% of the extracellular concentration. At pH 7.4, uptake was both passive- and carrier-mediated, but as the pH became more acidic, the uptake was exclusively passive. The intracellular concentration was not pH-dependent over 24 h. Uptake was dependent upon temperature but not the presence of foetal calf serum. Intracellular disposition in zymogen A-stimulated and unstimulated cells was throughout all compartments of the cell, but was higher in the nucleus and cell sap. Phagosomes of stimulated cells contained higher level of the antibiotic. Efflux from THP-1 monocytes was complete between 3 and 4 h. After 1 h treatment with zymogen A, THP-1 monocytes demonstrated an increase in intracellular acidity, protein kinase C, SOD and NAG activities, and NO, H(2)O(2), TNFalpha and IL-1 release over the 1st h. After 2-4 h the pH became alkaline, activities of NADPH reductase, NAG and cathepsin were reduced, and the release of NO, H(2)O(2), TNFalpha and IL-6 were suppressed. Protein synthesis and killing of the bacteria was evident in bacteria kept in monocyte-free medium and those phagocytized by the THP-1 monocytes moderately at 2 h, but more significantly at 24 h. The early killing of the bacteria appears to be a cidal mechanism whereas later, a standard bacteriostatic mechanism was evident. Nevertheless, suppression of these chemical mediators and hydrolytic enzyme activities would reduce the infection and the spread to adjacent areas.
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PMID:Disposition and intracellular activity of azithromycin in human THP-1 acute monocytes. 1243 70

Cultured human THP-1 monocytes were exposed to serial concentrations of gemifloxacin over 4 h after pre-stimulation with zymogen A for 1 h or Staphylococcus aureus for 2 h. The following parameters were assessed: pH, phagocytosis, c-AMP, NO, TNFalpha, IL-1, IL-6, IL-8 and H2O2 levels, enzyme activities of protein kinase C, NADPH oxidase, SOD, gluthathion reductase, NAG and cathepsin D as well as lipid peroxidation. The reversiblity of these changes was determined in the presence of known blockers of the phagocytic process. The effects of gemifloxacin on DNA synthesis and killing of S. aureus was assessed in bacteria alone and in those bacteria phagocytosed by THP-1 monocytes over 24 h. Gemifloxacin in stimulated THP-1 monocytes over the first 30 min caused an increase in c-AMP, NO, H2O2 and TNFalpha levels and protein kinase C, NADPH oxidase, glutathione reductase, NAG and cathepsin D activities. The pH became more acidic and phagocytosis was stimulated. These parameters were reversed at 1 h and continued to decline until 4 h. Lipid peroxidation was at the highest levels at 1 h and IL-8 levels at 2 h. DNA synthesis and bacterial growth were suppressed at 2 h in both S. aureus alone and bacteria phagocytosed by THP-1 monocytes. These effects were at a higher magnitude at 24 h. Gemifloxacin initiates a phagocyticidal effect of THP-1 monocytes at an early time of 30 min which plays a role in killing bacteria but a higher magnitude of killing of bacteria occurs later by a standard static mechanism. This early action of gemifloxacin should decrease the spread of infection and the inflammatory response since the tissue destruction process was attenuated at 4 h.
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PMID:In vitro anti-inflammatory effects and immunomodulation by gemifloxacin in stimulated human THP-1 monocytes. 1549 55

Analysis of non-histocompatibility leucocyte antigen (HLA) functional genomics, together with conventional risk factors in haematopoietic stem cell transplantation (HSCT) can lead to predicting outcome in HLA-matched sibling transplant recipients. Polymorphisms of cytokine genes including tumour necrosis factor alpha, interleukin-10, interferon gamma and interleukin (IL)-6, associate with more severe acute graft-versus-host disease (aGvHD). Donor genotype for IL-1 receptor antagonist (IL-1Ra) has been associated with reduced aGvHD severity. Other genotypes (patient IL-1Ra, IL-6 and donor IL-1 alpha) have been associated with chronic GvHD, or overall survival (Vitamin D receptor and oestrogen receptor). Polymorphisms within genes associated with host defence/inflammatory responses (mannose binding lectin genes, myeloperoxidase genes and the FC gamma receptors) have been associated with infections. Polymorphisms of pharmacogenes, such as methylenetetrahydrofolate-reductase, have been associated with aGvHD and other post-transplant complications. The NOD2 gene polymorphism, associated with Crohn's disease, has been shown to be associated with risk of gut GvHD. The majority of the studies have been carried out in single centre HLA-matched sibling cohorts and in relatively few matched unrelated donor transplants. This review gives an overall perspective of the current field of non-HLA genetics with regard to HSCT outcome, clinical relevance and potential application of the results to clinical management of HSCT.
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PMID:Genetic polymorphisms predicting the outcome of bone marrow transplants. 1556 51

Ceramide is a pro-apoptotic lipid messenger that induces oxidative stress and may mediate apoptosis in cerebral endothelial cells (CECs) induced by TNF-alpha/cycloheximide, lipopolysaccharide, oxidized LDL, IL-1, and amyloid peptide. Exposure of CECs to C2 ceramide for 12 h caused cell death in a concentration-dependent manner, with a LC50 of 30 microM. Statins are inhibitors of 3-hydroxyl-3-methyl coenzyme A reductase which is the rate-limiting enzyme for cholesterol biosynthesis. Pretreatment with pravastatin at 20 microM for 16 h substantially attenuated ceramide cytotoxicity in mouse CECs. Increases in vascular endothelial growth factor (VEGF) expression were detected within 1-3 h after pravastatin treatment. This pravastatin action was accompanied by the activation of hypoxia-inducible factor-1 (HIF-1), a transcription factor known to activate VEGF expression. These results raise the possibility that pravastatin may protect CECs against ceramide-induced death via the HIF-VEGF cascade.
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PMID:Pravastatin attenuates ceramide-induced cytotoxicity in mouse cerebral endothelial cells with HIF-1 activation and VEGF upregulation. 1596 81


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