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- 저자 : Balducci (검색결과 4 건)
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BALDUCCI-SILANO, PINA L.,SUZUKI, KOICHI,OHTA, MASANORI,SAITO, JUN,OHMORI, MASAYUKI,MONTANI, VALERIA,NAPOLITANO, GIORGIO,SHONG, MINHO,TANIGUCHI, SHIN-ICHI,PIETRARELLI, MICHELE,LAVARONI, STEFANO,MORI, A 충남대학교 생물공학연구소 1999 생물공학연구지 Vol.7 No.-
The single strand binding protein (SSBP-1) is a positive regulator of TSH receptor gene expression and binds to an element with a GXXXXG motif. The S box of the mouse major histocompatibility classⅡ gene has multiple GXXXXG motifs and can also bind SSBP-1. The S box is one of four highly conserved elements on the 5'-flanking region of classⅡ genes that are necessary for interferon-γ (IFNγ) to overcome the normally suppressed state of the gene and induce aberrant classⅡ expression. In this report we show that SSBP-1, when overexpressed in FRTL-5 thyroid cells, is a positive regulator of human leukocyte antigen (HLA)-DRα classⅡ gene expression, as is IFNγ or the classⅡ trans-activator (CIITA). This is evidenced by increased exogenous promoter activity, increased endogenous RNA levels, and increased endogenous antigen expression after transfecting full-length SSBP-1 complementary DNA together with a HLA-DRα promoter-reporter gene chimera into TSH-treated FRTL-5 thyroid cells whose endogenous SSBP-1 levels are low. IFNγ reverses the ability of TSH to decrease endogenous SSBP-1 RNA levels. Also, whereas SSBP-1 transfection does not cause any increase in IFNγ-induced exogenous promoter activity, transfection of SSBP-1 and CIITA additively increases endogenous classⅡ RNA levels to levels measured in cells treated with IFNγ. Further, competition studies show that SSBP-1 binding is necessary for formation of the double strand protein/DNA complexes that are seen in electrophoretic mobility shift assays when the classⅡ 5'-flanking region is incubated with extracts from IFNγ-treated FRTL-5 cells and that have been previously associated with IFNγ-induced aberrant classⅡ expression. These data suggest that SSBP-1 is involved in the action of IFNγ to overcome the normally suppressed state of the classⅡ gene; it functions together with CIITA, whose expression is independently increased by IFNγ. The effect of SSBP-1 as a positive regulator of classⅡ promoter activity is lost in cells maintained without TSH, in which endogenous SSBP-1 RNA levels are already high in the absence of aberrant classⅡ gene expression. These data suggest that high levels of endogenous SSBP-1 are insufficient to cause aberrant classⅡ expression, but, rather, TSH or IFNγ treatment additionally modulates the cell, albeit differently, such that transfected or endogenous SSBP-1, respectively, can express its positive regulatory activity. The effect of TSH is consistent with reports indicating that TSH enhances the ability of IFNγ to increase classⅡ gene expression despite the fact IFNγ increases endogenous SSBP-1 to only the same levels as in cells untreated with TSH. Finally, the effect of SSBP-1 as a positive regulator is lost when GXXXXG motifs, which exist on both the coding and noncoding strands of the S box, are mutated. Consistent with this, mutation and oligonucleotide competition studies show that GXXXXG motifs are necessary for either strand of the S box to bind protein/DNA complexes containing SSBP-1 in FRTL-5 cell extracts or to bind to recombinant SSBP-1. They also suggest that the SSBP-1-binding sites on either strand of the HLA-DRα S box are functionally distinct. We conclude from these data that the positive regulatory action of SSBP-1 on classⅡ gene expression involves GXXXXG motifs on each strand of the highly conserved S box of the classⅡ 5'-flanking region. As SSBP-1 is modulated by IFNγ and is involved in classⅠ and TSH receptor as well as classⅡ gene expression in FRTL-5 cells, the sum of the data supports the hypotheses that common transcription factors regulate all three genes, and their altered activities may contribute to the development of autoimmunity. (Endocrinology 139: 2300-2313, 1998)
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Dehydroepiandrosterone and cortisol concentrations in the cerebrospinal fluid of dogs
Mongillo, Paolo,Bernardini, Marco,Prana, Elisa,Balducci, Federica,Gabai, Gianfranco,Marinelli, Lieta The Korean Society of Veterinary Science 2017 大韓獸醫學會誌 Vol.57 No.1
Concentrations of cortisol, dehydroepiandrosterone and dehydroepiandrosterone-sulfate were measured by performing radioimmunoassay of the cerebrospinal fluid of 68 dogs diagnosed with idiopathic epilepsy or inflammatory, degenerative, or non-neurological disease. No steroid concentration differences were found among diagnoses. Dehydroepiandrosterone and dehydroepiandrosterone-sulfate concentrations were higher in males than in females and dehydroepiandrosterone-sulfate decreased with increasing age. No sex or age effects were observed on cortisol or hormone ratios. Although limited to a relatively small sample, our results show sex- and age-dependent variations in these neurosteroid concentrations in cerebrospinal fluid. The role of such variations in the pathophysiology of the dog brain warrants further investigation.
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