Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.99.3 (PRE)
 1,923 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammation is associated in some tissues with diminished responsiveness to steroid hormone action. We hypothesized that proinflammatory cytokines alter steroid hormone sensitivity, in part, by reducing levels of key nuclear receptor coactivators. Treatment of cultured human uterine smooth muscle cells (UtSMC) with TNF-alpha significantly reduced mRNA for the coactivators, SRC-1 (42%, P<0.01) and 2 (47%, P<0.03), and diminished the respective protein levels, but did not significantly alter the mRNAs encoding SRC-3, CBP and the corepressors, NCoR and SMRT; or progesterone receptor protein levels. To assess TNF-alpha effects on steroid hormone-mediated transcriptional activity, UtSMC were transfected with progesterone receptor B (PR-B) and a model PRE2-luciferase reporter construct. Transfected UtSMC were treated with progesterone alone or in the presence of TNF-alpha, and assayed for luciferase activity. TNF-alpha (10 ng/ml) diminished progesterone-stimulated PR-B-mediated transactivation by approximately 60% (P<0.02). The TNF-alpha-dependent decrease in PRE-luciferase activity was fully prevented by cotransfection with SRC-2, and partially prevented with exogenous SRC-1. In conclusion, TNF-alpha impairs progesterone-stimulated PR-B-mediated transactivation, and these effects appear to be due, in part, to reduced expression of SRC-1 and -2, which is a novel mechanism by which inflammation can functionally block steroid hormone action.
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PMID:Tumor necrosis factor-alpha suppresses the expression of steroid receptor coactivator-1 and -2: a possible mechanism contributing to changes in steroid hormone responsiveness. 1523 21

Exercise affects t-cell cytokine production. Whether or not these effects are caused by circulating factors associated with physical activity (e.g., inflammatory mediators, acidosis) is unknown. To investigate this, we incubated sera (10%), obtained from 16 young-adults before (PRE) and after (END) 30-min of exercise, with commercially available Jurkat cells, a t-lymphocyte model, that, of course, had never been exposed to an exercise milieu. After 1 and 6h in culture, we measured in the supernatant four cytokines (each known to be altered by exercise and involved in disease pathophysiology): IL-2, TGF-beta1, TNF-alpha, and IL-1ra. Cell proliferation was assessed with proliferating nuclear cell antigen (PNCA). Statistical analysis consisted of a linear mixed model for repeated measurement. There was no effect of exercise on t-cell production of either TGF-beta1 or IL-1ra. In contrast, both IL-2 (p=0.025) and TNF-alpha (p=0.031) production was significantly suppressed in sera from the exercising participants. The suppression of these two cytokines occurred despite the fact that PNCA significantly increased (p=0.0004) in the END serum. In conclusion, exercise alters circulating factors that can, subsequently, influence t-cell cytokine production in vitro.
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PMID:Serum from exercising humans suppresses t-cell cytokine production. 1791 19

To complete a successful liver transplantation (LTx) from non-heart-beating donors (NHBD), it is necessary to both improve the energy status in liver grafts and to reduce the exposure to free radicals. This study investigated the effects of short perfusion with oxygenated buffer on the grafts prior to cold preservation. In addition, the effects of the antioxidant, biliverdin, for reduction of free radicals was investigated. Male Wistar rats were used. Livers were retrieved, preserved in UW solution, and perfused for 60 min with oxygenated Krebs-Henseleit solution. Rats were allocated to six groups as follows (n=5): (i) control group-no warm ischemia (WI) and cold preservation, (ii) HBD group--no WI with cold preservation for 6 h; (iii) NHBD group--with 30 min of WI and cold preservation, (iv) NM group--with WI including nafamostat mesilate infusion before cardiac arrest and cold preservation; (v) PRE group--with WI, 30-min pre-cold preservation perfusion with oxygenated buffer after cardiac arrest, and cold preservation, (vi) BV group-with the same treatment as the PRE group plus the addition of biliverdin to the pre-cold preservation perfusion. The portal flow volume, bile production, AST, and TNF-alpha in perfusate, energy charge (EC), and ATP level in the tissue, and histological findings were investigated. The portal flow volume in the NM, PRE, and BV groups were higher than in the NHBD group. The bile production in the PRE and BV groups were also higher than in the NHBD group. The EC and ATP level of the BV group after reperfusion were higher than those of the NHBD group. Pre-cold preservation perfusion and addition of biliverdin to perfusate improved viability of grafts from NHBD. The results indicate that the preservation of the energy status and microcirculation of the graft is important for successful LTx from NHBD.
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PMID:The significance of preserving the energy status and microcirculation in liver grafts from non-heart-beating donor. 1846 47

The aim of this study was to investigate plasma IL-6, TNF-alpha, leptin and ghrelin concentrations during high-volume training. Eight trained male rowers participated. Fasting blood was sampled before (T1) and after (T2) increased training volume and after recovery period (T3). Two-hour rowing was performed at T1, T2 and at T3 with blood samples before, POST and POST 30'. Decrease in fasting leptin was observed at T2 (from 1.31 (0.53) to 0.93 (0.27) ng ml(-1); P < 0.05). Leptin was also significantly decreased at POST and POST 30 exercise compared to PRE test at T2. At T2 POST 30' leptin was significantly lower compared to corresponding value at T1. There were no significant post-exercise changes in ghrelin at T2 compared to T1 and T3. TNF-alpha was significantly increased POST exercise only at T2. In conclusion, high-volume training causes alterations of post exercise leptin and TNF-alpha, while increases in ghrelin are down regulated.
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PMID:The influence of increased training volume on cytokines and ghrelin concentration in college level male rowers. 1866 87