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Pesquisa : D04.210.500.745.745.654.339 [Categoria DeCS]
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[PMID]:28911177
[Au] Autor:Fletcher EK; Morgan J; Kennaway DR; Bienvenu LA; Rickard AJ; Delbridge LMD; Fuller PJ; Clyne CD; Young MJ
[Ad] Endereço:Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia.
[Ti] Título:Deoxycorticosterone/Salt-Mediated Cardiac Inflammation and Fibrosis Are Dependent on Functional CLOCK Signaling in Male Mice.
[So] Source:Endocrinology;158(9):2906-2917, 2017 Sep 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Activation of the mineralocorticoid receptor (MR) promotes inflammation, fibrosis, and hypertension. Clinical and experimental studies show that MR antagonists have significant therapeutic benefit for all-cause heart failure; however, blockade of renal MRs limits their widespread use. Identification of key downstream signaling mechanisms for the MR in the cardiovascular system may enable development of targeted MR antagonists with selectivity for pathological MR signaling and lower impact on physiological renal electrolyte handling. One candidate pathway is the circadian clock, the dysregulation of which is associated with cardiovascular diseases. We have previously shown that the circadian gene Per2 is dysregulated in hearts with selective deletion of cardiomyocyte MR. We therefore investigated MR-mediated cardiac inflammation and fibrosis in mice that lack normal regulation and oscillation of the circadian clock in peripheral tissues, that is, CLOCKΔ19 mutant mice. The characteristic cardiac inflammatory/fibrotic response to a deoxycorticosterone (DOC)/salt for 8 weeks was significantly blunted in CLOCKΔ19 mice when compared with wild-type mice, despite a modest increase at "baseline" for fibrosis and macrophage number in CLOCKΔ19 mice. In contrast, cardiac hypertrophy in response to DOC/salt was significantly greater in CLOCKΔ19 vs wild-type mice. Markers for renal inflammation and fibrosis were similarly attenuated in the CLOCKΔ19 mice given DOC/salt. Moreover, increased CLOCK expression in H9c2 cardiac cells enhanced MR-mediated transactivation of Per1, suggesting cooperative signaling between these transcription factors. This study demonstrates that the full development of MR-mediated cardiac inflammation and fibrosis is dependent on intact signaling by the circadian protein CLOCK.
[Mh] Termos MeSH primário: Proteínas CLOCK/genética
Desoxicorticosterona/farmacologia
Coração/efeitos dos fármacos
Miocardite/induzido quimicamente
Miocárdio/patologia
Cloreto de Sódio/farmacologia
[Mh] Termos MeSH secundário: Animais
Proteínas CLOCK/fisiologia
Células Cultivadas
Fibrose/induzido quimicamente
Fibrose/genética
Masculino
Camundongos
Camundongos Endogâmicos CBA
Camundongos Transgênicos
Ratos
Receptores de Mineralocorticoides/fisiologia
Transdução de Sinais/efeitos dos fármacos
Transdução de Sinais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Mineralocorticoid); 40GP35YQ49 (Desoxycorticosterone); 451W47IQ8X (Sodium Chloride); EC 2.3.1.48 (CLOCK Proteins); EC 2.3.1.48 (Clock protein, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1210/en.2016-1911


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[PMID]:28281299
[Au] Autor:Khatri Y; Schifrin A; Bernhardt R
[Ad] Endereço:Institute of Biochemistry, Saarland University, Saarbrücken, Germany.
[Ti] Título:Investigating the effect of available redox protein ratios for the conversion of a steroid by a myxobacterial CYP260A1.
[So] Source:FEBS Lett;591(8):1126-1140, 2017 Apr.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Since cytochromes P450 are external monooxygenases, available surrogate redox partners have been used to reconstitute the P450 activity. However, the effect of various ratios of P450s and the redox proteins have not been extensively studied so far, although different combinations of the redox partners have shown variations in substrate conversion. To address this issue, CYP260A1 was reconstituted with various ratios of adrenodoxin and adrenodoxin reductase to convert 11-deoxycorticosterone, and the products were characterized by NMR. We show the effect of the available redox protein ratios not only on the P450 catalytic activity but also on the product pattern.
[Mh] Termos MeSH primário: Adrenodoxina/metabolismo
Proteínas de Bactérias/metabolismo
Desoxicorticosterona/metabolismo
Ferredoxina-NADP Redutase/metabolismo
Modelos Moleculares
Myxococcales/enzimologia
Ácido Retinoico 4 Hidroxilase/metabolismo
Esteroide Hidroxilases/metabolismo
[Mh] Termos MeSH secundário: Adrenodoxina/genética
Animais
Ácido Ascórbico/metabolismo
Proteínas de Bactérias/genética
Biocatálise
Catalase/metabolismo
Desoxicorticosterona/análogos & derivados
Desoxicorticosterona/química
Ferredoxina-NADP Redutase/genética
Depuradores de Radicais Livres/metabolismo
Peróxido de Hidrogênio/química
Espectroscopia de Ressonância Magnética
Estrutura Molecular
NADP/metabolismo
Oxirredução
Proteínas Recombinantes/metabolismo
Estereoisomerismo
Esteroide Hidroxilases/genética
Superóxido Dismutase/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (11-deoxycorticosterone-1-ene); 0 (Bacterial Proteins); 0 (Free Radical Scavengers); 0 (Recombinant Proteins); 12687-22-8 (Adrenodoxin); 40GP35YQ49 (Desoxycorticosterone); 53-59-8 (NADP); BBX060AN9V (Hydrogen Peroxide); EC 1.11.1.6 (Catalase); EC 1.14.- (Steroid Hydroxylases); EC 1.14.14.1 (Retinoic Acid 4-Hydroxylase); EC 1.15.1.1 (Superoxide Dismutase); EC 1.18.1.2 (Ferredoxin-NADP Reductase); PQ6CK8PD0R (Ascorbic Acid)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170311
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12619


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[PMID]:28216153
[Au] Autor:Gilbert C; Provost PR; Tremblay Y
[Ad] Endereço:Reproduction, Mother and Youth Health, Centre de recherche du CHU de Québec, Québec, QC, Canada; Centre de Recherche en Reproduction, Développement et Santé Intergénérationnelle (CRDSI), Faculté de Médecine, Université Laval, Québec, QC, Canada.
[Ti] Título:Dynamic modulation of Cyp21a1 (21-hydroxylase) expression sites in the mouse developing lung.
[So] Source:J Steroid Biochem Mol Biol;168:102-109, 2017 Apr.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:21-hydroxylase is expressed in the developing lung where it is proposed as a local source of glucocorticoids playing important roles in lung development. We have studied the precise sites of Cyp21a1 expression in the developing mouse lung from the pseudoglandular stage (gestation day (GD) 15.5) to the alveolar stage (postnatal day (PND) 15) by in situ hybridization. Cyp21a1-mRNA was found mainly in epithelial cells from GD 15.5 to PND 5, but the precise site of expression shifted from the distal epithelium during the pseudoglandular and the canalicular stages including the distal epithelium without lumina, to the proximal epithelium and the wall of developing saccules during the perinatal period (GD 19.5 and PND 0), and to the wall of developing saccules and septa, most probably in type I pneumonocytes (PTI), on PND 5. Cyp21a1 expression changed from PTI cells to capillary endothelial cells of the same distal structures during alveolarization. The mesenchyme was generally negative. Endothelial cells forming large vessels were negative. However the tunica adventitia surrounding arteries was Cyp21a1-positive, while several veins were surrounded by a Cyp21a1-positive layer. In conclusion, Cyp21a1 remains expressed in the most distal structure of the developing lung even though these structures are changing, but its expression is not restricted to these areas. Taken together, our data show the highly dynamic modulation of Cyp21a1 expression sites, consistent with the evolving structures of the developing lung.
[Mh] Termos MeSH primário: Perfilação da Expressão Gênica
Regulação da Expressão Gênica no Desenvolvimento
Pulmão/embriologia
Esteroide 21-Hidroxilase/metabolismo
[Mh] Termos MeSH secundário: Células Epiteliais Alveolares/citologia
Animais
Desoxicorticosterona/metabolismo
Células Epiteliais/metabolismo
Epitélio/metabolismo
Feminino
Glucocorticoides/metabolismo
Seres Humanos
Hibridização In Situ
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Alvéolos Pulmonares/embriologia
Receptores de Glucocorticoides/metabolismo
Esteroide 21-Hidroxilase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glucocorticoids); 0 (Receptors, Glucocorticoid); 40GP35YQ49 (Desoxycorticosterone); EC 1.14.14.16 (Cyp21a1 protein, mouse); EC 1.14.14.16 (Steroid 21-Hydroxylase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170704
[Lr] Data última revisão:
170704
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170221
[St] Status:MEDLINE


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[PMID]:28185934
[Au] Autor:Mandiki SN; Milla S; Robles SN; Kestemont P
[Ad] Endereço:Research Unit of Environmental and Evolutionary Biology (URBE), University of Namur, Rue de Bruxelles 61, B-5000 Namur, Belgium. Electronic address: robert.mandiki@unamur.be.
[Ti] Título:Corticosteroids deeply depress the in vitro steroidogenic capacity of Eurasian perch ovary at the end of the reproductive cycle.
[So] Source:Gen Comp Endocrinol;245:44-54, 2017 May 01.
[Is] ISSN:1095-6840
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Corticosteroids play positive or negative role in the reproductive mechanisms of many fish species but the physiological contexts relating to such biphasic actions are not well defined. In the present study we investigated to what extent corticosteroids (cortisol-Co, 11-deoxycorticosterone-DOC) hormones may interfere with the steroidogenic capacity of Eurasian perch ovarian tissues, and we tested whether the negative effects of corticosteroids may be mitigated by potential stimulating endocrine factors, namely insulin-like growth factor-1 (IGF), human chorionic gonadotropin (HCG) or thyroid hormones (Triidothyronine-T3, thyroxine-T4). Ovarian tissues from six maturing fish at late vitellogenesis developmental stage (LVO) or at the start of the final meiotic oocyte maturation (FMO) were incubated during 6h in Cortland medium containing various endocrine compounds. Both corticosteroids drastically suppressed aromatase activity (AA) and sex-steroid production, namely 17-ß estradiol (E2), 17α-20ß-dihydroxy-4-pregnen-3-one (DHP) and testosterone (T). HCG significantly prevented the suppression of both AA and sex-steroid production by low and high cortisol doses, but a lesser AA protection was observed in the case of DOC. The protection of DHP and T productions by HCG from the negative effects by the two corticosteroids was higher at FMO than at LVO stage. IGF or thyroid hormone treatments were lesser effective or ineffective in mitigating the suppression of AA or sex-steroid production by cortisol. The results suggest that an increase in cortisol or DOC such as after mild or high stress intensity may inhibit drastically the ovarian steroidogenic capacity whatever the final oocyte maturation stage in percid fish by hampering AA and sex-steroid production. That inhibition may be partly mitigated by gonadotropins but not IGF nor thyroid hormones, especially at final meiotic oocyte maturation stage.
[Mh] Termos MeSH primário: Desoxicorticosterona/farmacologia
Hormônios Esteroides Gonadais/metabolismo
Hidrocortisona/farmacologia
Percas/fisiologia
[Mh] Termos MeSH secundário: Animais
Aromatase/genética
Aromatase/metabolismo
Feminino
Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos
Hormônios Esteroides Gonadais/genética
Seres Humanos
Oócitos/crescimento & desenvolvimento
Ovário/efeitos dos fármacos
Ovário/metabolismo
Receptor IGF Tipo 1/farmacologia
Tiroxina/farmacologia
Técnicas de Cultura de Tecidos
Tri-Iodotironina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gonadal Steroid Hormones); 06LU7C9H1V (Triiodothyronine); 40GP35YQ49 (Desoxycorticosterone); EC 1.14.14.1 (Aromatase); EC 2.7.10.1 (Receptor, IGF Type 1); Q51BO43MG4 (Thyroxine); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170211
[St] Status:MEDLINE


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[PMID]:28163026
[Au] Autor:Nikolaus J; Nguyen KT; Virus C; Riehm JL; Hutter M; Bernhardt R
[Ad] Endereço:Department of Biochemistry, Saarland University, Campus B2.2, 66123 Saarbrücken, Germany.
[Ti] Título:Engineering of CYP106A2 for steroid 9α- and 6ß-hydroxylation.
[So] Source:Steroids;120:41-48, 2017 Apr.
[Is] ISSN:1878-5867
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CYP 106A2 from Bacillus megaterium ATCC 13368 has been described as a 15ß-hydroxylase showing also minor 11α-, 9α- and 6ß-hydroxylase activity for progesterone conversion. Previously, mutant proteins with a changed selectivity towards 11α-OH-progesterone have already been produced. The challenge of this work was to create mutant proteins with a higher regioselectivity towards hydroxylation at positions 9 and 6 of the steroid molecule. 9α-hydroxyprogesterone exhibits pharmaceutical importance, because it is a useful intermediate in the production of physiologically active substances which possess progestational activity. Sixteen mutant proteins were selected from a library containing mutated proteins created by a combination of site-directed and saturation mutagenesis of active site residues. Four mutant proteins out of these catalyzed the conversion of progesterone to 9α-OH-progesterone as a main product. For further optimization site-directed mutagenesis was performed. The introduction of seven mutations (D217V, A243V, A106T, F165L, T89N, T247V or T247W) into these four mutant proteins led to 28 new variants, which were also used for an in vivo conversion of progesterone. The best mutant protein, F165L/A395E/G397V, showed a ten-fold increase in the selectivity towards progesterone 9α-hydroxylation compared with the wild type CYP106A2. Also 6ß-OH-progesterone is a pharmaceutically important compound, especially as intermediate for the production of drugs against breast cancer. For the rational design of mutant proteins with 6ß-selectivity, docking of the 3D-structure of CYP106A2 with progesterone was performed. The introduction of three mutations (T247A, A243S, F173A) led to seven new mutant proteins. Clone A243S showed the greatest improvement in 6ß-selectivity being more than ten-fold. Finally, an in vivo conversion of 11-deoxycorticosterone (DOC), testosterone and cortisol with the best five mutant proteins displaying 9α- or 6ß-hydroxylation, respectively, of progesterone was performed to investigate whether the introduced mutations also effected the conversion of other substrates.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Sistema Enzimático do Citocromo P-450/metabolismo
[Mh] Termos MeSH secundário: Adrenodoxina/química
Adrenodoxina/metabolismo
Desoxicorticosterona/química
Desoxicorticosterona/metabolismo
Hidroxilação
Mutação
Progesterona/química
Progesterona/metabolismo
Estereoisomerismo
Esteroide Hidroxilases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 12687-22-8 (Adrenodoxin); 40GP35YQ49 (Desoxycorticosterone); 4G7DS2Q64Y (Progesterone); 9035-51-2 (Cytochrome P-450 Enzyme System); EC 1.14.- (15beta-hydroxylase CYP106A2, Bacillus megaterium); EC 1.14.- (Steroid Hydroxylases); EC 1.14.99.- (steroid 9-alpha-hydroxylase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170830
[Lr] Data última revisão:
170830
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170207
[St] Status:MEDLINE


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[PMID]:28125600
[Au] Autor:Geddes RI; Hayashi K; Bongers Q; Wehber M; Anderson IM; Jansen AD; Nier C; Fares E; Farquhar G; Kapoor A; Ziegler TE; VadakkadathMeethal S; Bird IM; Atwood CS
[Ad] Endereço:Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Wisconsin, United States of America.
[Ti] Título:Conjugated Linoleic Acid Administration Induces Amnesia in Male Sprague Dawley Rats and Exacerbates Recovery from Functional Deficits Induced by a Controlled Cortical Impact Injury.
[So] Source:PLoS One;12(1):e0169494, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Long-chain polyunsaturated fatty acids like conjugated linoleic acids (CLA) are required for normal neural development and cognitive function and have been ascribed various beneficial functions. Recently, oral CLA also has been shown to increase testosterone (T) biosynthesis, which is known to diminish traumatic brain injury (TBI)-induced neuropathology and reduce deficits induced by stroke in adult rats. To test the impact of CLA on cognitive recovery following a TBI, 5-6 month old male Sprague Dawley rats received a focal injury (craniectomy + controlled cortical impact (CCI; n = 17)) or Sham injury (craniectomy alone; n = 12) and were injected with 25 mg/kg body weight of Clarinol® G-80 (80% CLA in safflower oil; n = 16) or saline (n = 13) every 48 h for 4 weeks. Sham surgery decreased baseline plasma progesterone (P4) by 64.2% (from 9.5 ± 3.4 ng/mL to 3.4 ± 0.5 ng/mL; p = 0.068), T by 74.6% (from 5.9 ± 1.2 ng/mL to 1.5 ± 0.3 ng/mL; p < 0.05), 11-deoxycorticosterone (11-DOC) by 37.5% (from 289.3 ± 42.0 ng/mL to 180.7 ± 3.3 ng/mL), and corticosterone by 50.8% (from 195.1 ± 22.4 ng/mL to 95.9 ± 2.2 ng/mL), by post-surgery day 1. CCI injury induced similar declines in P4, T, 11-DOC and corticosterone (58.9%, 74.6%, 39.4% and 24.6%, respectively) by post-surgery day 1. These results suggest that both Sham surgery and CCI injury induce hypogonadism and hypoadrenalism in adult male rats. CLA treatment did not reverse hypogonadism in Sham (P4: 2.5 ± 1.0 ng/mL; T: 0.9 ± 0.2 ng/mL) or CCI-injured (P4: 2.2 ± 0.9 ng/mL; T: 1.0 ± 0.2 ng/mL, p > 0.05) animals by post-injury day 29, but rapidly reversed by post-injury day 1 the hypoadrenalism in Sham (11-DOC: 372.6 ± 36.6 ng/mL; corticosterone: 202.6 ± 15.6 ng/mL) and CCI-injured (11-DOC: 384.2 ± 101.3 ng/mL; corticosterone: 234.6 ± 43.8 ng/mL) animals. In Sham surgery animals, CLA did not alter body weight, but did markedly increase latency to find the hidden Morris Water Maze platform (40.3 ± 13.0 s) compared to saline treated Sham animals (8.8 ± 1.7 s). In CCI injured animals, CLA did not alter CCI-induced body weight loss, CCI-induced cystic infarct size, or deficits in rotarod performance. However, like Sham animals, CLA injections exacerbated the latency of CCI-injured rats to find the hidden MWM platform (66.8 ± 10.6 s) compared to CCI-injured rats treated with saline (30.7 ± 5.5 s, p < 0.05). These results indicate that chronic treatment of CLA at a dose of 25 mg/kg body weight in adult male rats over 1-month 1) does not reverse craniectomy- and craniectomy + CCI-induced hypogonadism, but does reverse craniectomy- and craniectomy + CCI-induced hypoadrenalism, 2) is detrimental to medium- and long-term spatial learning and memory in craniectomized uninjured rats, 3) limits cognitive recovery following a moderate-severe CCI injury, and 4) does not alter body weight.
[Mh] Termos MeSH primário: Amnésia/fisiopatologia
Lesões Encefálicas/fisiopatologia
Disfunção Cognitiva/fisiopatologia
Ácidos Linoleicos Conjugados/efeitos adversos
Recuperação de Função Fisiológica/efeitos dos fármacos
[Mh] Termos MeSH secundário: Amnésia/sangue
Amnésia/induzido quimicamente
Animais
Lesões Encefálicas/sangue
Córtex Cerebral/efeitos dos fármacos
Córtex Cerebral/lesões
Córtex Cerebral/fisiopatologia
Cognição/efeitos dos fármacos
Disfunção Cognitiva/sangue
Corticosterona/sangue
Desoxicorticosterona/sangue
Modelos Animais de Doenças
Hipocampo/efeitos dos fármacos
Hipocampo/lesões
Hipocampo/fisiopatologia
Ácidos Linoleicos Conjugados/administração & dosagem
Masculino
Aprendizagem em Labirinto/efeitos dos fármacos
Memória/efeitos dos fármacos
Progesterona/sangue
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Linoleic Acids, Conjugated); 40GP35YQ49 (Desoxycorticosterone); 4G7DS2Q64Y (Progesterone); W980KJ009P (Corticosterone)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171121
[Lr] Data última revisão:
171121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170127
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0169494


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[PMID]:27813053
[Au] Autor:Hofmann A; Peitzsch M; Brunssen C; Mittag J; Jannasch A; Frenzel A; Brown N; Weldon SM; Eisenhofer G; Bornstein SR; Morawietz H
[Ad] Endereço:Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany.
[Ti] Título:Elevated Steroid Hormone Production in the db/db Mouse Model of Obesity and Type 2 Diabetes.
[So] Source:Horm Metab Res;49(1):43-49, 2017 Jan.
[Is] ISSN:1439-4286
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Obesity and type 2 diabetes have become a major public health problem worldwide. Steroid hormone dysfunction appears to be linked to development of obesity and type 2 diabetes and correction of steroid abnormalities may offer new approaches to therapy. We therefore analyzed plasma steroids in 15-16 week old obese and diabetic mice using liquid chromatography-tandem mass spectrometry. Lean served as controls. mice developed obesity, hyperglycemia, hyperleptinemia, and hyperlipidemia. Hepatic triglyceride storage was increased and adiponectin and pancreatic insulin were lowered. Aldosterone, corticosterone, 11-deoxycorticosterone, and progesterone were respectively increased by 3.6-, 2.9-, 3.4, and 1.7-fold in mice compared to controls. Ratios of aldosterone-to-progesterone and corticosterone-to-progesterone were respectively 2.0- and 1.5-fold higher in mice. Genes associated with steroidogenesis were quantified in the adrenal glands and gonadal adipose tissues. In adrenals, , , , , , and were all significantly increased in mice compared with controls. In adipose tissue, no or transcripts were detected and no differences in , , , or expression were found between and mice. In conclusion, the present study showed an elevated steroid hormone production and adrenal steroidogenesis in the model of obesity and type 2 diabetes.
[Mh] Termos MeSH primário: Corticosteroides/metabolismo
Diabetes Mellitus Experimental/metabolismo
Diabetes Mellitus Tipo 2/metabolismo
Hormônios Esteroides Gonadais/metabolismo
Obesidade/metabolismo
[Mh] Termos MeSH secundário: Corticosteroides/sangue
Aldosterona/sangue
Aldosterona/metabolismo
Animais
Corticosterona/sangue
Corticosterona/metabolismo
Desoxicorticosterona/sangue
Desoxicorticosterona/metabolismo
Diabetes Mellitus Experimental/complicações
Diabetes Mellitus Tipo 2/patologia
Hormônios Esteroides Gonadais/sangue
Seres Humanos
Masculino
Camundongos
Camundongos Obesos
Obesidade/complicações
Progesterona/sangue
Progesterona/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adrenal Cortex Hormones); 0 (Gonadal Steroid Hormones); 40GP35YQ49 (Desoxycorticosterone); 4964P6T9RB (Aldosterone); 4G7DS2Q64Y (Progesterone); W980KJ009P (Corticosterone)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170327
[Lr] Data última revisão:
170327
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161105
[St] Status:MEDLINE
[do] DOI:10.1055/s-0042-116157


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[PMID]:27743930
[Au] Autor:Modgil A; Parakala ML; Ackley MA; Doherty JJ; Moss SJ; Davies PA
[Ad] Endereço:Tufts University School of Medicine, Department of Neuroscience, 136 Harrison Ave, Boston, MA 02111, USA.
[Ti] Título:Endogenous and synthetic neuroactive steroids evoke sustained increases in the efficacy of GABAergic inhibition via a protein kinase C-dependent mechanism.
[So] Source:Neuropharmacology;113(Pt A):314-322, 2017 Feb.
[Is] ISSN:1873-7064
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The neuroactive steroid (NAS) tetrahydrodeoxycorticosterone (THDOC) increases protein kinase C (PKC) mediated phosphorylation of extrasynaptic GABA receptor (GABA R) subunits leading to increased surface expression of α4/ß3 subunit-containing extrasynaptic GABA Rs, leading to a sustained increase in GABA R tonic current density. Whether other naturally occurring and synthetic NASs share both an allosteric and metabotropic action on GABA Rs is unknown. Here, we examine the allosteric and metabotropic properties of allopregnanolone (ALLO), and synthetic NASs SGE-516 and ganaxolone. ALLO, SGE-516, and ganaxolone all allosterically enhanced prototypical synaptic and extrasynaptic recombinant GABA Rs. In dentate gyrus granule cells (DGGCs) all three NASs, when applied acutely, allosterically enhanced tonic and phasic GABAergic currents. In separate experiments, slices were exposed to NASs for 15 min, and then transferred to a steroid naïve recording chamber followed by ≥ 30 min wash before tonic currents were measured. A sustained increase in tonic current was observed following exposure to ALLO, or SGE-516 and was prevented by inhibiting PKC with GF 109203X. No increase in tonic current was observed with exposure to ganaxolone. In agreement with the observations of an increased tonic current, the NASs ALLO and SGE-516 increased the phosphorylation and surface expression of the ß3 subunit-containing GABA Rs. Our studies demonstrate that neuroactive steroids have differential abilities to induce sustained increases in the efficacy of tonic inhibition by promoting GABA R phosphorylation and membrane trafficking dependent on PKC activity.
[Mh] Termos MeSH primário: Desoxicorticosterona/análogos & derivados
Inibição Neural/fisiologia
Pregnanolona/farmacologia
Proteína Quinase C/metabolismo
Receptores de GABA-A/metabolismo
[Mh] Termos MeSH secundário: Animais
Células CHO
Cricetinae
Cricetulus
Desoxicorticosterona/farmacologia
Inibidores Enzimáticos/farmacologia
Células HEK293
Hipocampo
Seres Humanos
Indóis/farmacologia
Masculino
Maleimidas/farmacologia
Camundongos
Camundongos Endogâmicos C57BL
Inibição Neural/efeitos dos fármacos
Técnicas de Cultura de Órgãos
Proteína Quinase C/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (Indoles); 0 (Maleimides); 0 (Receptors, GABA-A); 40GP35YQ49 (Desoxycorticosterone); 4AB717DP4A (tetrahydrodeoxycorticosterone); BXO86P3XXW (Pregnanolone); EC 2.7.11.13 (Protein Kinase C); L79H6N0V6C (bisindolylmaleimide I)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170902
[Lr] Data última revisão:
170902
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161105
[St] Status:MEDLINE


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[PMID]:27663860
[Au] Autor:Hisamichi M; Kamijo-Ikemori A; Sugaya T; Ichikawa D; Natsuki T; Hoshino S; Kimura K; Shibagaki Y
[Ad] Endereço:Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
[Ti] Título:Role of angiotensin II type 1a receptor in renal injury induced by deoxycorticosterone acetate-salt hypertension.
[So] Source:FASEB J;31(1):72-84, 2017 Jan.
[Is] ISSN:1530-6860
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to investigate the in vivo role of angiotensin II type 1a (AT1a) receptor in renal damage as a result of hypertension by using transgenic mice with AT1a receptor gene disruption. Transgenic mice that express human liver-type fatty acid binding protein (L-FABP) with or without disruption of the AT1a receptor gene (L-FABP AT1a , and L-FABP AT1a , respectively) were used with urinary L-FABP as an indicator of tubulointerstitial damage. Those female mice were administered subcutaneously deoxycorticosterone acetate (DOCA)-salt tablets plus drinking water that contained 1% saline for 28 d after uninephrectomy. In L-FABP AT1a mice that received DOCA-salt treatment, hypertension was induced and slight expansion of glomerular area, glomerular sclerosis, and tubulointerstitial damage were observed. In L-FABP AT1a mice that received DOCA-salt treatment, hypertension was similarly induced and the degree of glomerular damage was significantly more severe than in L-FABP AT1a -DOCA mice. Urinary L-FABP levels were significantly higher in L-FABP AT1a -DOCA mice compared with those in L-FABP AT1a -DOCA mice. Hydralazine treatment significantly attenuated renal damage that was found in L-FABP AT1a -DOCA mice along with a reduction in blood pressure. In summary, activation of the AT1a receptor may contribute to maintenance of the glomerular structure against hypertensive renal damage.-Hisamichi, M., Kamijo-Ikemori, A., Sugaya, T., Ichikawa, D., Natsuki, T., Hoshino, S., Kimura, K., Shibagaki, Y. Role of angiotensin II type 1a receptor in renal injury induced by deoxycorticosterone acetate-salt hypertension.
[Mh] Termos MeSH primário: Desoxicorticosterona/toxicidade
Hipertensão/induzido quimicamente
Nefropatias/induzido quimicamente
Receptor Tipo 1 de Angiotensina/metabolismo
Cloreto de Sódio/toxicidade
[Mh] Termos MeSH secundário: Animais
Proteínas de Ligação a Ácido Graxo/genética
Proteínas de Ligação a Ácido Graxo/metabolismo
Feminino
Fibrose/etiologia
Fibrose/patologia
Regulação da Expressão Gênica/fisiologia
Seres Humanos
Nefropatias/patologia
Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética
Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo
Camundongos
Camundongos Knockout
Camundongos Transgênicos
Receptor Tipo 1 de Angiotensina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (FABP1 protein, human); 0 (Fatty Acid-Binding Proteins); 0 (Low Density Lipoprotein Receptor-Related Protein-2); 0 (Lrp2 protein, mouse); 0 (Receptor, Angiotensin, Type 1); 40GP35YQ49 (Desoxycorticosterone); 451W47IQ8X (Sodium Chloride)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160925
[St] Status:MEDLINE
[do] DOI:10.1096/fj.201600684RR


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[PMID]:27650398
[Au] Autor:Bowen TS; Eisenkolb S; Drobner J; Fischer T; Werner S; Linke A; Mangner N; Schuler G; Adams V
[Ad] Endereço:Department of Internal Medicine and Cardiology, Leipzig University Heart Center, Leipzig, Germany bows@med.uni-leipzig.de.
[Ti] Título:High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice.
[So] Source:FASEB J;31(1):60-71, 2017 Jan.
[Is] ISSN:1530-6860
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hypertension is a key risk factor for heart failure, with the latter characterized by diaphragm muscle weakness that is mediated in part by increased oxidative stress. In the present study, we used a deoxycorticosterone acetate (DOCA)-salt mouse model to determine whether hypertension could independently induce diaphragm dysfunction and further investigated the effects of high-intensity interval training (HIIT). Sham-treated (n = 11), DOCA-salt-treated (n = 11), and DOCA-salt+HIIT-treated (n = 15) mice were studied over 4 wk. Diaphragm contractile function, protein expression, enzyme activity, and fiber cross-sectional area and type were subsequently determined. Elevated blood pressure confirmed hypertension in DOCA-salt mice independent of HIIT (P < 0.05). Diaphragm forces were impaired by ∼15-20% in DOCA-salt vs. sham-treated mice (P < 0.05), but this effect was prevented after HIIT. Myosin heavy chain (MyHC) protein expression tended to decrease (∼30%; P = 0.06) in DOCA-salt vs. sham- and DOCA-salt+HIIT mice, whereas oxidative stress increased (P < 0.05). Enzyme activity of NADPH oxidase was higher, but superoxide dismutase was lower, with MyHC oxidation elevated by ∼50%. HIIT further prevented direct oxidant-mediated diaphragm contractile dysfunction (P < 0.05) after a 30 min exposure to H O- (1 mM). Our data suggest that hypertension induces diaphragm contractile dysfunction via an oxidant-mediated mechanism that is prevented by HIIT.-Bowen, T. S., Eisenkolb, S., Drobner, J., Fischer, T., Werner, S., Linke, A., Mangner, N., Schuler, G., Adams, V. High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice.
[Mh] Termos MeSH primário: Diafragma/patologia
Treinamento Intervalado de Alta Intensidade
Debilidade Muscular/prevenção & controle
Oxidantes/metabolismo
Condicionamento Físico Animal/fisiologia
[Mh] Termos MeSH secundário: Animais
Fenômenos Fisiológicos Cardiovasculares
Desoxicorticosterona/administração & dosagem
Desoxicorticosterona/farmacologia
Hipertensão
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Mineralocorticoides/administração & dosagem
Mineralocorticoides/farmacologia
Mitocôndrias/fisiologia
Contração Muscular/efeitos dos fármacos
Contração Muscular/fisiologia
Debilidade Muscular/metabolismo
Estresse Oxidativo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Mineralocorticoids); 0 (Oxidants); 40GP35YQ49 (Desoxycorticosterone)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160922
[St] Status:MEDLINE
[do] DOI:10.1096/fj.201600672R



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