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1.
BMC Anesthesiol ; 22(1): 376, 2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36471246

RESUMO

BACKGROUND: Electroconvulsive therapy (ECT) remains the mainstay treatment option for patients with psychiatric diseases, such as severe depression. Although various anesthetic techniques provide adequate therapeutic seizures, hyperventilation is a useful adjunct to augment seizure duration and improve seizure quality. We investigated how to efficiently use a facemask to accomplish protocolized hyperventilation and evaluate its effect on ECT seizure. METHODS: We studied 60 patients aged ≥18 years who underwent ECT. The patients were divided into two groups according to the technique of facemask ventilation used: the one-handed (n = 30) and two-handed (n = 30) groups. Following anesthesia induction under preoxygenation conditions, hyperventilation induced hypocapnia in the one-handed facemask group with manual bag ventilation was compared to that in the two-handed facemask group with assisted pressure-controlled ventilation. Ictal and peri-ictal electroencephalogram parameters and cardiovascular responses were monitored and compared between the one-handed and two-handed groups. RESULTS: The two-handed technique demonstrated better electroencephalogram regularity and minimized cardiovascular stress compared to the one-handed technique. These conclusions come from the fact that the one-handed technique induced a substantial volume of leaks around the facemask (201.7 ± 98.6 mL/breath), whereas minimal leaks (25.8 ± 44.6 mL/breath) with stabler and higher ventilation rate led to greater inhaled minute ventilation in the two-handed group (the one-handed group, 9.52 ± 3.94 L/min; the two-handed group, 11.95 ± 2.29 L/min; p <  0.005). At the end of ECT treatment, all parameters of blood pressure and heart rate increased significantly in both groups equally, with lower SpO2 and more ST-segment depression on the electrocardiogram in the one-handed group. Comparing baseline values before anesthesia, ECT treatment significantly depressed ST-segment in both groups, while the degree of depression in ST-segment increased significantly in the one-handed group compared to that in the two-handed group. CONCLUSIONS: End-tidal carbon dioxide monitoring for hyperventilation can reliably ensure hypocapnia only in the two-handed group. In ECT, the two-handed technique assisted by pressure-controlled ventilation is an effective and practical method for hyperventilation to induce adequate therapeutic seizures. While, the two-handed group with sufficient preoxygenation did not cause more cardiovascular stress than the one-handed group. TRIAL REGISTRATION: UMIN Clinical Trials Registry 000046544, Date of registration 05/01/2022.


Assuntos
Eletroconvulsoterapia , Humanos , Adolescente , Adulto , Eletroconvulsoterapia/métodos , Hiperventilação/complicações , Hipocapnia/etiologia , Máscaras/efeitos adversos , Convulsões
2.
J Anesth ; 34(2): 281-285, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020373

RESUMO

PURPOSE: The Dräger Perseus A500 (Perseus) anesthetic workstation has been designed with a lower internal volume. We evaluated the recovery time following general anesthesia using the Perseus workstation compared with that using the conventional Dräger Fabius Plus workstation. METHODS: Following approval by our institutional research ethics committee, 50 patients receiving elective surgery under general anesthesia were enrolled in the study. Written informed consent was obtained from each patient. The patients were divided into the Perseus group and a control group. The Perseus anesthesia workstation was used for the Perseus group, and the Fabius Plus was used for the control group. General anesthesia was maintained with a 4.2% end-tidal concentration of desflurane, remifentanil, fentanyl, and regional anesthesia. After the surgical procedure, the administration of desflurane was discontinued. The inspiratory and expiratory desflurane concentration, time taken for patients to open their eyes, and the time taken to extubate the trachea after discontinuation of anesthetics were recorded. RESULTS: The inspiratory and expiratory desflurane concentration after the administration of desflurane was discontinued was lower in the Perseus group. Moreover, the time taken for patients to open their eyes was statistically significantly quicker in the Perseus group when compared with the control group: 284 ± 60 vs 325 ± 43 s, respectively. The time taken for extubation was also statistically significantly quicker in the Perseus group when compared with the control group: 350 ± 67 vs 388 ± 62 s, respectively. CONCLUSIONS: We demonstrate in this study that Perseus enables the faster wash-out of anesthetics and faster recovery of patients after general anesthesia.


Assuntos
Anestésicos Inalatórios , Isoflurano , Período de Recuperação da Anestesia , Anestesia Geral , Anestésicos Intravenosos , Desflurano , Humanos
3.
J Anesth ; 29(2): 289-91, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25138819

RESUMO

We report a case of posterior wall hematoma formation in the internal jugular vein after the puncture of central vein. An 82-year-old woman was scheduled for laparotomy for an abdominal incisional hernia. After induction of general anesthesia, we performed central venous catheterization via the right internal jugular vein under ultrasound guidance in the short-axis view and out-of plane technique. The ultrasound view after insertion of a guide-wire revealed a hematoma-like space on the posterior wall of the vein. We removed and reinserted the guide-wire. This time, insertion of the wire and catheter was uneventful. Seven days after the surgery, no hematoma-like space was found in the vein. The malposition of the guide-wire was detected before dilation, which enabled us to avoid complications in this case. We should note that the confirmation of guide-wire placement in the vein is important during ultrasound-guided central venous catheterization.


Assuntos
Cateterismo Venoso Central/efeitos adversos , Veias Jugulares/lesões , Idoso de 80 Anos ou mais , Catéteres/efeitos adversos , Feminino , Hematoma/diagnóstico por imagem , Hematoma/etiologia , Hérnia Abdominal/cirurgia , Humanos , Veias Jugulares/diagnóstico por imagem , Ultrassonografia de Intervenção
4.
Am J Case Rep ; 23: e938357, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36471649

RESUMO

BACKGROUND Intraoperative tracheal rupture due to endotracheal intubation is a rare but serious complication that requires prompt responses. Transoral laser microsurgery is effective for dissection of laryngeal and nasopharyngeal lesions, and a laser-resistant endotracheal tube is therefore commonly used under general anesthesia. CASE REPORT We present the case of a 69-year-old man in whom a rare complication involving endotracheal tube tip dislodgement during transoral laser surgery led to iatrogenic tracheal rupture. We used a Laser-Flex cuffed endotracheal tube, which is a non-inflammable, armored stainless-steel tube with a Murphy eye. Repeated mobilization of the laryngoscope blade and excessive neck extension for adequate laryngeal exposure during surgery may have led to significant soft tissue swelling and tube tip displacement, inducing tracheal rupture with the keen edge of the Murphy eye. At the end of the surgical procedure, subcutaneous emphysema was observed in the right anterior neck. Computed tomography revealed subcutaneous emphysema and pneumomediastinum without esophageal injury or mediastinitis. The injury was 1 cm in length, with wall involvement to a depth to the muscular wall in the membranous trachea at a point 2 cm proximal to the carina, in which we could position the alternative endotracheal tube distal to the tracheal rupture. After conservative treatment, the patient was extubated and mechanical ventilation was ceased. CONCLUSIONS During transoral laser laryngeal and nasopharyngeal surgery, dislodgement of the laser-resistant endotracheal tube tip can lead to iatrogenic tracheal rupture. In this case, injury during application of a Laser-Flex cuffed endotracheal tube with a Murphy eye, was followed by conservative treatment. This treatment achieved a successful outcome.


Assuntos
Enfisema Subcutâneo , Doenças da Traqueia , Masculino , Humanos , Idoso , Traqueia/cirurgia , Traqueia/lesões , Ruptura/etiologia , Ruptura/cirurgia , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/métodos , Doenças da Traqueia/complicações , Enfisema Subcutâneo/etiologia , Lasers , Doença Iatrogênica
5.
PLoS One ; 17(5): e0268568, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35584094

RESUMO

PURPOSE: To analyze the cause of prolonged recovery from general anesthesia with remimazolam. METHODS: We studied 65 patients under general anesthesia with remimazolam. According to time to extubation, patients were divided into short period (SP) (n = 34, < 15 min) and long period (LP) (n = 31, ≥ 15 min) groups. Variables affecting time to extubation such as age, sex, height, body weight, body mass index (BMI), plasma albumin concentration, ASA class, duration of surgery, and total duration of general anesthesia, and total dose of remimazolam were compared between SP and LP groups. At the end of remimazolam infusion and upon extubation, predictive remimazolam concentrations were calculated using pharmacokinetic/pharmacodynamic three compartment modeling. RESULTS: LP group showed significantly higher BMI, older age, and lower plasma albumin concentration compared with those of SP group. Logistic regression analysis showed that the probability of time to extubation of ≥ 15 min was higher in patients with BMI greater than 22.0 kg/m2 (AUC 0.668, 95% CI 0.533‒0.803), ages older than 79.0 years (AUC 0.662, 95% CI 0.526‒0.798), and plasma albumin concentrations lower than 3.60 g/dl (AUC 0.720, 95% CI 0.593‒0.847). LP group showed significantly lower predicted remimazolam concentration than SP group upon extubation despite no difference in concentration between both groups at the end of infusion. Pharmacological analysis estimates that LP group is more sensitive to remimazolam than SP group through amplified responses. CONCLUSIONS: Lower remimazolam doses should be considered for the overweight patients, elderly, and those with lower plasma albumin concentration.


Assuntos
Extubação , Hipnóticos e Sedativos , Idoso , Benzodiazepinas , Humanos , Albumina Sérica
6.
Environ Sci Technol ; 45(6): 2086-92, 2011 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-21322630

RESUMO

Speciation of iodine in a soil-water system was investigated to understand the mechanism of iodine mobility in surface environments. Iodine speciation in soil and pore water was determined by K-edge XANES and HPLC-ICP-MS, respectively, for samples collected at a depth of 0-12 cm in the Yoro area, Chiba, Japan. Pore water collected at a 0-6 cm depth contained 50%-60% of organic iodine bound to dissolved organic matter, with the other portion being I(-). At a 9-12 cm depth, 98% of iodine was in the form of dissolved I(-). In contrast, XANES analysis revealed that iodine in soil exists as organic iodine at all depths. Iodine mapping of soil grains was obtained using micro-XRF analysis, which also indicated that iodine is bound to organic matter. The activity of laccase, which has the ability to oxidize I(-) to I(2), was high at the surface of the soil-water layer, suggesting that iodide oxidizing enzymes can promote iodine organification. The distribution coefficient of organic iodine in the soil-water system was more than 10-fold greater than that of iodide. Transformation of inorganic iodine to organic iodine plays an important role in iodine immobilization, especially in a surface soil-water system.


Assuntos
Água Doce/química , Hidrocarbonetos Iodados/química , Iodetos/química , Poluentes do Solo/química , Poluentes Químicos da Água/química , Meia-Vida , Hidrocarbonetos Iodados/análise , Iodetos/análise , Japão , Solo/química , Poluentes do Solo/análise , Poluentes Químicos da Água/análise , Espectroscopia por Absorção de Raios X
7.
J Recept Signal Transduct Res ; 30(6): 484-92, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20684663

RESUMO

Angiotensinogen (AGT), mainly produced in the liver, is the precursor of angiotensin II, an important regulator of blood pressure and electrolyte homeostasis. We previously showed, in hepatoma-derived HepG2 cells that a hepatocyte nuclear factor 4 (HNF4) potentiated human AGT (hAGT) promoter activity and identified its binding sites (termed regions C and J) in the hAGT promoter region. We also showed in transgenic mouse (TgM) that the hAGT is abundantly expressed in the kidney where the level of endogenous mouse AGT (mAGT) expression is low. To elucidate molecular mechanisms of the AGT gene activation in the kidney, we first investigated the HNF4 and AGT expression in the mouse kidney. Northern blot, in situ hybridization and immunohistochemical analyses revealed that the hAGT and HNF4 were both expressed in the proximal tubular (PT) cells of the kidney. We then transfected the hAGT reporter constructs into immortalized mouse PT (mProx) cells and found that regions C and J contributed additively to the HNF4-potentiated hAGT promoter activity. Curiously, no obvious HNF4 binding motif was found in the corresponding region of the mAGT promoter and co-transfected HNF4 failed to activate this promoter in neither HepG2 nor mProx cells. These results suggest that the high-level hAGT expression in the TgM kidney is, at least in part, due to a presence of high-affinity HNF4 binding sites in its promoter.


Assuntos
Angiotensinogênio/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Regiões Promotoras Genéticas , Angiotensinogênio/metabolismo , Animais , Sítios de Ligação/genética , Fator 4 Nuclear de Hepatócito/genética , Humanos , Rim/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Transgênicos
9.
Anal Sci ; 24(3): 405-9, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18332551

RESUMO

Environmental behavior of iodine is of great importance especially related to the release of radioiodine from the processing of nuclear fuel, nuclear accidents, etc. To understand the fate of radioactive iodine in soil-water systems, it is necessary to establish a speciation method of iodine in soil. XANES is one of the most important candidates and we compared the performance of L(III)-edge and K-edge XANES for this purpose. In particular, fluorescence XANES with a multi-element semiconductor detector is essential for the measurement of XANES spectra for trace amounts of iodine in natural soil samples. When comparing L(III)- and K-edges, L(III)-edge XANES can be useful for the speciation due to its ability to distinguish various iodine species in their XANES spectra. However, at L(III)-edge measuring iodine L(alpha) emission, the proximity of its energy to those of Ca K(alpha) and K(beta1) causes a large contribution of background X-rays in the XANES spectra, since Ca is a major element in soil. Thus, it was concluded that K-edge XANES is more useful than L(III)-edge for the speciation of iodine in natural soils owing to its lower detection limit. The K-edge XANES was successfully applied to the speciation of natural iodine in a soil sample (iodine concentration: 55.8 mg/kg), showing that iodine is present in the sample as organo-iodine species incorporated in humic substances.


Assuntos
Compostos de Iodo/análise , Iodo/análise , Poluentes do Solo/química , Substâncias Húmicas/análise , Sensibilidade e Especificidade , Análise Espectral/métodos , Raios X
10.
J Clin Anesth ; 36: 88-89, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28183582

RESUMO

We report the application of ultrasound prescans for spinal anesthesia to morbid obesity patient. A 38-year-old woman with a body mass index (BMI) of 50 (weight: 110 kg; height: 148 cm) was scheduled to undergo pilonidal cyst resection at the bottom of the tailbone. Spinal anesthesia was selected for the procedure, because the patient's position during the surgery was prone and the patient had morbid obesity. To determine the spinal needle insertion point and the distance between the skin and dura, we planned to use ultrasound. The transverse view of the patient's lumbar spine showed the posterior dura, transverse process, and posterior vertebral body below the thick fat tissue. At this point, spinal anesthesia was successfully performed. Pre-insertion ultrasound guidance for spinal anesthesia was useful in this morbidly obese patient with a BMI of 50.


Assuntos
Raquianestesia/métodos , Vértebras Lombares/diagnóstico por imagem , Obesidade Mórbida/diagnóstico por imagem , Seio Pilonidal/cirurgia , Adulto , Índice de Massa Corporal , Feminino , Humanos , Obesidade Mórbida/complicações , Decúbito Ventral , Ultrassonografia de Intervenção/métodos
11.
Am J Case Rep ; 17: 259-63, 2016 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-27086704

RESUMO

BACKGROUND: The clinical manifestations of eosinophilic gastroenteritis are nonspecific and vary depending on which layer of the gastrointestinal tract is involved. Computed tomography (CT) is valuable for detecting and characterizing gastrointestinal wall abnormalities. CASE REPORT: We report a case of eosinophilic gastroenteritis that formed a chamber in the rigid duodenal wall of a 67-year-old woman. Abdominal CT showed symmetrical wall thickening of the gastric antrum and duodenal bulb, and the bowel walls consisted of 2 continuous, symmetrically stratified layers. There was a chamber mimicking a giant ulcer at the orifice of the descending duodenum. Eosinophilic inflammation was present through this rigid wall of the descending duodenum, accompanied by perienteric inflammation, which infiltrated the anterior pararenal space, gall bladder, and right colic flexure. Gastrointestinal endoscopy showed spotty erosions and reddish mucosa, with the edematous gastric antrum and duodenal bulb narrowed at their lumens. Just beyond the supraduodenal angle at the orifice of the descending duodenum, there was a chamber with only minor mucosal changes, and it was not a duodenal ulcer. Endoscopic biopsy of the duodenum showed intramucosal eosinophilic infiltration. Treatment with prednisolone resulted in normalization of radiologic and endoscopic abnormalities. CONCLUSIONS: We present a case of eosinophilic gastroenteritis with both mucosal and muscular involvement. CT imaging and endoscopic examination confirmed the diagnosis.


Assuntos
Enterite/diagnóstico , Eosinofilia/diagnóstico , Gastrite/diagnóstico , Idoso , Diagnóstico Diferencial , Úlcera Duodenal/diagnóstico , Endoscopia Gastrointestinal , Feminino , Humanos , Tomografia Computadorizada por Raios X
12.
Int J Mol Med ; 13(5): 729-33, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15067378

RESUMO

The renin-angiotensin system plays a key role in the regulation of blood pressure. Angiotensinogen (ANG), mainly synthesized in the liver, is the first substrate of renin-angiotensin system. We had previously found that hepatocyte nuclear factor 4 (HNF-4) dramatically activates the human ANG promoter. It is generally known that HNF-4 and peroxisome proliferator-activated receptor alpha (PPARalpha) bind to response elements composed of two core motifs, RG(G/T)TCA, or a closely related sequence separated by 1 nucleotide (DR1 element). To examine whether or not PPARalpha activates the human ANG promoter, we used the reporter gene containing the sequence from -1222 to +44 of the human ANG gene promoter. PPARalpha and RXR heterodimer activated this promoter, and the PPARalpha responsive region was the same site that we had previously mapped as a binding site for HNF-4. Although the human ANG promoter was not induced by PPARalpha ligand bezafibrate in HepG2 cells, this reporter gene was inducible by bezafibrate treatment in HeLa cells, which do not express endogenous HNF-4. We suspected that the high level expression of HNF-4 in HepG2 cells might interfere with the effect of bezafibrate on the human ANG promoter. To confirm this model, we cotransfected HNF-4 expression vector with PPARalpha expression vector into HeLa cells. The bezafibrate-dependent activation of the ANG promoter was inhibited by HNF-4. These results suggest that PPARalpha and HNF-4 competitively affect the human ANG promoter through the C region.


Assuntos
Angiotensinogênio/genética , Regulação da Expressão Gênica , PPAR alfa/metabolismo , Regiões Promotoras Genéticas/genética , Bezafibrato/farmacologia , Ligação Competitiva , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dimerização , Regulação da Expressão Gênica/efeitos dos fármacos , Genes Reporter/genética , Fator 4 Nuclear de Hepatócito , Humanos , Ligantes , PPAR alfa/antagonistas & inibidores , PPAR alfa/genética , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Elementos de Resposta/genética , Receptores X de Retinoides/metabolismo , Deleção de Sequência/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacos , Transfecção
13.
Int J Mol Med ; 12(2): 161-7, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12851711

RESUMO

The ubiquitous basic helix-loop-helix transcription factor USFs encoded by two distinct genes (USF1 and USF2) recognize a core motif, CACGTG, termed E box and regulate the expression of a variety of genes. USF1 and USF2 proteins form homo- and heterodimers to bind the target core motif DNA. Here, we report the molecular cloning and functional characterization of a novel alternative splicing variant of human USF1 (hUSF1), termed USF1/BD. Compared with USF1 wild-type (wt), USF1/BD lacks the N-terminal transactivation domain. Cloning and characterization of the hUSF1 genomic region revealed that USF1/BD is generated by excising the sequence corresponding to a part of exon 4. In transiently transfected cells, USF1/BD was localized in the nucleus and repressed the promoter activity of the human angiotensinogen gene. In vitro translated USF1/BD possessed DNA binding activity as a homodimer and a heterodimer with USF1 (wt). These results suggest that USF1/BD plays a role as a modulator of USF1 to control the expression of target genes.


Assuntos
Processamento Alternativo , Proteínas de Ligação a DNA , Fatores de Transcrição/genética , Angiotensinogênio/genética , Animais , Sequência de Bases , Sítios de Ligação , Células Cultivadas , Clonagem Molecular , Códon de Terminação , Dimerização , Elementos E-Box , Éxons , Regulação da Expressão Gênica , Sequências Hélice-Alça-Hélice , Humanos , Camundongos , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Estrutura Terciária de Proteína , Homologia de Sequência do Ácido Nucleico , Fatores de Transcrição/metabolismo , Fatores Estimuladores Upstream
14.
J Biol Chem ; 283(47): 32432-41, 2008 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-18805788

RESUMO

Glucokinase (GK) and glucose-6-phosphatase (G6Pase) regulate rate-limiting reactions in the physiologically opposed metabolic cascades, glycolysis and gluconeogenesis, respectively. Expression of these genes is conversely regulated in the liver in response to fasting and feeding. We explored the mechanism of transcriptional regulation of these genes by nutritional condition and found that reciprocal function of HNF-4 and Foxo1 plays an important role in this process. In the GK gene regulation, Foxo1 represses HNF-4-potentiated transcription of the gene, whereas it synergizes with HNF-4 in activating the G6Pase gene transcription. These opposite actions of Foxo1 concomitantly take place in the cells under no insulin stimulus, and such gene-specific action was promoter context-dependent. Interestingly, HNF-4-binding elements (HBEs) in the GK and G6Pase promoters were required both for the insulin-stimulated GK gene activation and insulin-mediated G6Pase gene repression. Indeed, mouse in vivo imaging showed that mutating the HBEs in the GK and G6Pase promoters significantly impaired their reactivity to the nutritional states, even in the presence of intact Foxo1-binding sites (insulin response sequences). Thus, in the physiological response of the GK and G6Pase genes to fasting/feeding conditions, Foxo1 distinctly decodes the promoter context of these genes and differently modulates the function of HBE, which then leads to opposite outcomes of gene transcription.


Assuntos
Jejum , Privação de Alimentos , Fatores de Transcrição Forkhead/metabolismo , Regulação Enzimológica da Expressão Gênica , Glucoquinase/metabolismo , Glucose-6-Fosfatase/metabolismo , Fator 4 Nuclear de Hepatócito/metabolismo , Transcrição Gênica , Animais , Proteína Forkhead Box O1 , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
15.
J Biol Chem ; 279(22): 23158-65, 2004 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-15047713

RESUMO

Bile acid homeostasis is tightly controlled by the feedback mechanism in which an atypical orphan nuclear receptor (NR) small heterodimer partner (SHP) inactivates several NRs such as liver receptor homologue-1 and hepatocyte nuclear factor 4. Although NRs have been implicated in the transcriptional regulation of gluconeogenic genes, the effect of bile acids on gluconeogenic gene expression remained unknown. Here, we report that bile acids inhibit the expression of gluconeogenic genes, including glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase, and fructose 1,6-bis phosphatase in an SHP-dependent fashion. Cholic acid diet decreased the mRNA levels of these gluconeogenic enzymes, whereas those of SHP were increased. Reporter assays demonstrated that the promoter activity of phosphoenolpyruvate carboxykinase and fructose 1,6-bis phosphatase via hepatocyte nuclear factor 4, or that of G6Pase via the forkhead transcription factor Foxo1, was down-regulated by treatment with chenodeoxicholic acid and with transfected SHP. Remarkably, Foxo1 interacted with SHP in vivo and in vitro, which led to the repression of Foxo1-mediated G6Pase transcription by competition with a coactivator cAMP response element-binding protein-binding protein. These findings reveal a novel mechanism by which bile acids regulate gluconeogenic gene expression via an SHP-dependent regulatory pathway.


Assuntos
Ácidos e Sais Biliares/metabolismo , Proteínas de Ligação a DNA/antagonistas & inibidores , Gluconeogênese/genética , Fosfoproteínas/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Animais , Linhagem Celular , Retroalimentação , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead , Regulação da Expressão Gênica , Fator 4 Nuclear de Hepatócito , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores Citoplasmáticos e Nucleares/genética , Fatores de Transcrição/genética
16.
J Biol Chem ; 278(7): 5427-32, 2003 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-12459554

RESUMO

The EWS gene when fused to transcription factors such as the ETS family ATF-1, Wilms' tumor-1, and nuclear orphan receptors upon chromosomal translocation is thought to contribute the development of Ewing sarcoma and several malignant tumors. Although EWS is predicted to be an RNA-binding protein, an inherent EWS nuclear function has not yet been elucidated. In this study, we found that EWS associates with a transcriptional co-activator CREB-binding protein (CBP) and the hypophosphorylated RNA polymerase II, which are included preferentially in the transcription preinitiation complex. These interactions suggest the potential involvement of EWS in gene transcription, leading to the hypothesis that EWS may function as a co-activator of CBP-dependent transcription factors. Based on this hypothesis, we investigated the effect of EWS on the activation of nuclear receptors that are activated by CBP. Of nuclear receptors examined, hepatocyte nuclear factor 4-dependent transcription was selectively enhanced by EWS but not by an EWS mutant defective for CBP binding. These results suggest that EWS as a co-activator requires CBP for hepatocyte nuclear factor 4-mediated transcriptional activation.


Assuntos
Proteínas de Ligação a DNA , Proteínas Nucleares/genética , Fosfoproteínas/genética , Proteína EWS de Ligação a RNA/genética , Transativadores/genética , Fatores de Transcrição/genética , Ativação Transcricional , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Proteína de Ligação a CREB , Linhagem Celular , Fator 4 Nuclear de Hepatócito , Humanos , Proteínas Nucleares/metabolismo , Proteína EWS de Ligação a RNA/metabolismo , Transativadores/metabolismo
17.
J Biol Chem ; 279(9): 7770-6, 2004 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-14672953

RESUMO

Bile acids function as transcriptional regulators for the genes important in bile acid synthesis and cholesterol homeostasis. In this study, we identified angiotensinogen (ANG), the precursor of vasoactive octapeptide angiotensin II, as a novel target gene of bile acids. In human ANG transgenic mice, administration of cholic acid resulted in the down-regulation of human ANG gene expression in the liver. ANG gene expression in HepG2 cells was also repressed by chenodeoxycholic acid. Because the expression of small heterodimer partner (SHP) mRNA was induced by chenodeoxycholic acid in HepG2 cells, we analyzed the effects of SHP on the human ANG promoter. Promoter mutation analysis demonstrated that SHP repressed human ANG promoter activity through the element, which has been previously determined as a binding site for hepatocyte nuclear factor-4 (HNF-4). SHP repressed human ANG promoter activity only when the HNF-4 expression vector was cotransfected in HeLa cells. Furthermore, we found that SHP bound to the HNF-4 N-terminal region including the DNA-binding domain and activation function-1 and that SHP prevented HNF-4 from binding to the human ANG promoter. These results suggest that bile acids negatively regulate the human ANG gene through the inhibitory effect of SHP on HNF-4.


Assuntos
Angiotensinogênio/genética , Ácidos e Sais Biliares/farmacologia , Proteínas de Ligação a DNA , Regulação da Expressão Gênica/efeitos dos fármacos , Fosfoproteínas/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/fisiologia , Fatores de Transcrição/antagonistas & inibidores , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Sítios de Ligação , Carcinoma Hepatocelular , Ácido Quenodesoxicólico/farmacologia , Ácido Cólico/farmacologia , DNA/metabolismo , Feminino , Expressão Gênica , Células HeLa , Fator 4 Nuclear de Hepatócito , Humanos , Fígado/química , Luciferases/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutagênese , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Regiões Promotoras Genéticas/genética , RNA Mensageiro/análise , Receptores Citoplasmáticos e Nucleares/genética , Proteínas Recombinantes de Fusão , Proteínas Recombinantes , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transfecção , Células Tumorais Cultivadas
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