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Registros recuperados: 5
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3D model of lamprey estrogen receptor with estradiol and 15[alpha]-hydroxy-estradiol Nature Precedings
Michael E. Baker; David J. Chang; Charlie Chandsawangbhuwana.
Lamprey, a basal vertebrate, contains orthologs of the estrogen receptor (ER), progesterone receptor and corticoid receptor. A perplexing property of lamprey is that 15[alpha]-hydroxy-steroids are active steroids. For example, 15[alpha]-hydroxy-estradiol [15[alpha]-OH-E2] is the estrogen, instead of estradiol (E2). To investigate how 15[alpha]-OH-E2 binds lamprey ER, we constructed a 3D model of the lamprey ER with E2 and 15[alpha]-OH-E2. Our 3D model shows that S[delta] on Met-409 can form a hydrogen bond with the 15[alpha]-hydroxyl on 15[alpha]-OH-E2. In human ER[alpha], the corresponding residue Ile-424 has a van der Waals contact with 15[alpha]-OH-E2. BLAST analysis of GenBank indicates that among vertebrate ERs, only lamprey ER contains a...
Tipo: Manuscript Palavras-chave: Developmental Biology; Ecology; Earth & Environment.
Ano: 2009 URL: http://precedings.nature.com/documents/2768/version/1
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Dibutyltin Disrupts Glucocorticoid Receptor Function and Impairs Glucocorticoid-induced Suppression of Cytokine Production Nature Precedings
Christel Gumy; Charlie Chandsawangbhuwana; Anna A. Dzyakanchuk; Denise V. Kratschmar; Michael E. Baker; Alex Odermatt.
_Background_. Organotins are highly toxic and widely distributed environmental chemicals. Dibutyltin (DBT) is used as stabilizer in the production of polyvinyl chloride plastics, and it is also the major metabolite formed from tributyltin (TBT) _in vivo_. DBT is immunotoxic, however, the responsible targets remain to be defined. Due to the importance of glucocorticoids in immune-modulation, we investigated whether DBT could interfere with glucocorticoid receptor (GR) function.
_Methodology_. We used HEK-293 cells transiently transfected with human GR as well as rat H4IIE hepatoma cells and native human macrophages and human THP-1 macrophages expressing endogenous receptor to study organotin effects on GR function. Docking of organotins was...
Tipo: Manuscript Palavras-chave: Immunology; Pharmacology; Bioinformatics.
Ano: 2008 URL: http://precedings.nature.com/documents/2312/version/1
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Hexose-6-phosphate dehydrogenase modulates the effect of inhibitors and alternative substrates of 11[beta]-hydroxysteroid dehydrogenase 1 Nature Precedings
Zoltán Balázs; Lyubomir G. Nashev; Charlie Chandsawangbhuwana; Michael E. Baker; Alex Odermatt.
Intracellular glucocorticoid reactivation is catalyzed by 11[beta]-hydroxysteroid dehydrogenase 1 (11[beta]-HSD1), which functions predominantly as a reductase in cells expressing hexose-6-phosphate dehydrogenase (H6PDH). We recently showed that the ratios of cortisone to cortisol and 7-keto- to 7-hydroxy-neurosteroids are regulated by 11[beta]-HSD1 and very much depend on co-expression with H6PDH, providing cosubstrate NADPH. Here, we investigated the impact of H6PDH on the modulation of 11[beta]-HSD1-dependent inter-conversion of cortisone and cortisol by inhibitors and alternative substrates. Using HEK-293 cells expressing 11[beta]-HSD1 or co-expressing 11[beta]-HSD1 and H6PDH, we observed significant differences of 11[beta]-HSD1 inhibition by natural...
Tipo: Manuscript Palavras-chave: Molecular Cell Biology; Pharmacology; Bioinformatics.
Ano: 2008 URL: http://precedings.nature.com/documents/2430/version/1
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Motif analysis of amphioxus, lamprey and invertebrate estrogen receptors and amphioxus and human estrogen-related receptors: Towards a better understanding of estrogen receptor evolution Nature Precedings
Michael E. Baker; Charlie Chandsawangbhuwana.
*Background.* The origins of steroid-dependent regulation of the vertebrate estrogen receptor (ER) are poorly understood. Genes with statistically significant sequence similarity to vertebrate ERs have been found in lamprey, a basal vertebrate, and amphioxus, a basal chordate. Motif analysis of these sequences provides an opportunity to investigate early events in the evolution of the ER.
*Results.* We used artificial intelligence-based software to construct twelve motifs specific to the estrogen-binding domain of ER[alpha] and ER[beta] in land vertebrates and teleosts. We mapped these ER-specific motifs onto the sequences of lamprey, amphioxus, invertebrate and selected vertebrate ERs and amphioxus, Ciona and human estrogen-related...
Tipo: Manuscript Palavras-chave: Cancer; Developmental Biology; Ecology; Evolutionary Biology.
Ano: 2008 URL: http://precedings.nature.com/documents/1542/version/2
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Motif analysis of amphioxus, lamprey and invertebrate estrogen receptors and amphioxus and human estrogen-related receptors: Towards a better understanding of estrogen receptor evolution Nature Precedings
Michael E. Baker; Charlie Chandsawangbhuwana.
*Background.* The origins of steroid-dependent regulation of the vertebrate estrogen receptor (ER) are poorly understood. Genes with statistically significant sequence similarity to vertebrate ERs have been found in lamprey, a basal vertebrate, and amphioxus, a basal chordate. Motif analysis of these sequences provides an opportunity to investigate early events in the evolution of the ER.
*Results.* We used artificial intelligence-based software to construct twelve motifs specific to the estrogen-binding domain of ER[alpha] and ER[beta] in land vertebrates and teleosts. We mapped these ER-specific motifs onto the sequences of lamprey, amphioxus, invertebrate and selected vertebrate ERs and amphioxus and human estrogen-related receptor...
Tipo: Manuscript Palavras-chave: Cancer; Developmental Biology; Ecology; Bioinformatics.
Ano: 2008 URL: http://precedings.nature.com/documents/1542/version/1
Registros recuperados: 5
Primeira ... 1 ... Última
 

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