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1.
Environ Res ; 231(Pt 3): 116266, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37257744

RESUMEN

In this study, the feasibility of Mg/Al layered double hydroxides (LDH) functionalized coffee ground waste biochars (LDHMgAl@CWGB) as a potential adsorbent to selectively recover phosphate (PO43-) and nitrate (NO3-) ions in aqueous phases and their consecutive uses as a slow-release fertilizer for stimulating the plant growth were identified. The higher adsorption capacity of PO43- and NO3- ions by LDHMgAl@CWGB (PO43- = 6.98 mgP/g, NO3- = 2.82 mgN/g) compared with pristine coffee ground waste biochars (CWGB; PO43- = 0.19 mgP/g, NO3- = 0.32 mgN/g) was mainly due to the incorporation of Mg/Al mixed oxides and Cl contents. Chemisorption and intra-particle mainly controlled the adsorptive recovery of PO43- and NO3- ions by CWGB and LDHMgAl@CWGB in aqueous phases and their adsorption toward CWGB and LDHMgAl@CWGB proceeded endothermically and spontaneously. The changes in the major adsorption mechanisms of PO43- and NO3- ions from ligand exchange (CWGB) to electrostatic surface complexation and anion-exchange (LDHMgAl@CWGB) supported the conclusion that the alternation of the surface features through Mg/Al LDH functionalization might improve selectivity and adsorption capacity of PO43- and NO3- ions onto CWGB under the co-existence of Cl-, SO42-, and HCO3- ions. Since PO43-- and NO3--loaded LDHMgAl@CWGB exhibited much higher seed germination, root and shoot growth rates of garden cress seeds (Lepidium sativum L) than other liquid and solid matrices, including 5 mgP/L PO43- and 5 mgN/L NO3-, 10 mgP/L PO43- and 10 mgN/L NO3-, and LDHMgAl@CWGB, it can be postulated that PO43-- and NO3--loaded LDHMgAl@CWGB could be practically applicable to the agricultural field as a slow-release fertilizer to facilitate the seed germination, root and shoot growth of the plants.


Asunto(s)
Nitratos , Fosfatos , Fertilizantes , Café , Hidróxidos , Agua , Adsorción , Cinética
2.
Environ Pollut ; 313: 120138, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36089142

RESUMEN

The adsorption of radioactive iodine, which is capable of presenting high mobility in aquatic ecosystems and generating undesirable health effects in humans (e.g., thyroid gland dysfunction), was comprehensively examined using pristine spent coffee ground biochar (SCGB) and bismuth-impregnated spent coffee ground biochar (Bi@SCGB) to provide valuable insights into the variations in the adsorption capacity and mechanisms after pretreatment with Bi(NO3)3. The greater adsorption of radioactive iodine toward Bi@SCGB (adsorption capacity (Qe) = 253.71 µg/g) compared to that for SCGB (Qe = 23.32 µg/g) and its reduced adsorption capability at higher pH values provide evidence that the adsorption of radioactive iodine with SCGB and Bi@SCGB is strongly influenced by the presence of bismuth materials and the electrostatic repulsion between their negatively charged surfaces and negatively charged radioactive iodine (IO3-). The calculated R2 values for the adsorption kinetics and isotherms support that chemisorption plays a crucial role in the adsorption of radioactive iodine by SCGB and Bi@SCGB in aqueous phases. The adsorption of radioactive iodine onto SCGB was linearly correlated with the contact time (h1/2), and the diffusion of intra-particle predominantly determined the adsorption rate of radioactive iodine onto Bi@SCGB (Cstage II (129.20) > Cstage I (42.33)). Thermodynamic studies revealed that the adsorption of radioactive iodine toward SCGB (ΔG° = -8.47 to -7.83 kJ/mol; ΔH° = -13.93 kJ/mol) occurred exothermically and that for Bi@SCGB (ΔG° = -15.90 to -13.89 kJ/mol; ΔH° = 5.88 kJ/mol) proceeded endothermically and spontaneously. The X-ray photoelectron spectroscopy (XPS) analysis of SCGB and Bi@SCGB before and after the adsorption of radioactive iodine suggest the conclusion that the change in the primary adsorption mechanism from electrostatic attraction to surface precipitation upon the impregnation of bismuth materials on the surfaces of spent coffee ground biochars is beneficial for the adsorption of radioactive iodine in aqueous phases.


Asunto(s)
Neoplasias de la Tiroides , Contaminantes Químicos del Agua , Adsorción , Bismuto , Carbón Orgánico/química , Café/química , Ecosistema , Humanos , Radioisótopos de Yodo , Cinética , Agua/química , Contaminantes Químicos del Agua/análisis
3.
Environ Res ; 199: 111346, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34019898

RESUMEN

The single adsorption of radioactive barium (Ba(II)), cobalt (Co(II)), and strontium (Sr(II)) ions using pristine (SCWB-P) and chemically activated spent coffee waste biochars with NaOH (SCWB-A) were thoroughly explored in order to provide deeper insights into the changes in their adsorption mechanisms through alkaline chemical activation. The greater removal efficiencies of SCWB-A (76.6-97.3%) than SCWB-P (45.6-75.2%) and the consistency between the adsorptive removal patterns (Ba(II) > Sr(II) > Co(II)) and oxygen bond dissociation enthalpies (BaO (562 kJ/mol) > SrO (426 kJ/mol) > CoO (397 kJ/mol)) of radioactive species supported the assumption that the adsorption removal of radioactive species with spent coffee waste biochars highly depended on the abundances of O-containing functional groups. The calculated R2 values of the pseudo-first-order (SCWB-P = 0.998-0.999; SCWB-A = 0.850-0.921) and pseudo-second-order kinetic models (SCWB-P = 0.988-0.998; SCWB-A = 0.935-0.966) are evident that the physisorption mainly controlled the adsorption of radioactive species toward SCWB-P and the chemisorption played a crucial role in their adsorptive removal with SCWB-A. From the calculated intra-particle diffusion, isotherm, thermodynamic parameters, it can be concluded that the intra-particle diffusion and monolayer adsorption primarily governed the adsorption of radioactive species using SCWB-P and SCWB-A, and their adsorption processes occurred spontaneously and endothermically. The dominant adsorption mechanism of spent coffee waste biochars was changed from physisorption (ΔH° of SCWB-P = 21.6-29.8 kJ/mol) to chemisorption (ΔH° of SCWB-A = 42.4-81.3 kJ/mol) through alkaline chemical activation. The distinctive M-OH peak in the O1s XPS spectra of SCWB-A directly corresponding to the decrease in the abundances of O-containing functional groups confirms again that the enrichment of O-containing functional groups markedly facilitated the adsorption removal of radioactive species by chemisorption occurred at the inner and outer surfaces of spent coffee waste biochars.


Asunto(s)
Estroncio , Contaminantes Químicos del Agua , Adsorción , Bario , Carbón Orgánico , Cobalto , Café , Iones , Cinética , Termodinámica , Contaminantes Químicos del Agua/análisis
4.
Environ Sci Pollut Res Int ; 28(30): 40623-40632, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32677012

RESUMEN

This study examined differences in the adsorption isotherms, kinetic equations, and thermodynamics of Sr2+ by biochar from spent coffee grounds (SCG) and powdered activated carbon (PAC). The specific surface area (957.6 m2/g) and pore volume (0.676 cm3/g) of PAC were much greater than those of SCG biochar (specific surface area = 11.0 m2/g, pore volume = 0.009 cm3/g). However, SCG biochar showed a higher maximum adsorption capacity of Sr2+ (Qmax = 51.81 mg/g) compared with PAC (Qmax = 32.79 mg/g) due to its abundance of O-containing functional groups. The negligible removal efficiencies of Sr2+ by SCG biochar and PAC under acidic conditions (pH = 1.0-3.0) are evidence that the electrostatic repulsion might hinder severely the adsorption of Sr2+ by the carbonaceous adsorbents. The higher R2 values of the pseudo-second-order model (R2 ≥ 0.999) compared with the pseudo-first-order model (R2 ≥ 0.815) suggest that chemisorption governed the removal of Sr2+ using SCG biochar and PAC. Furthermore, the better description of the adsorption behavior of Sr2+ by the Langmuir isotherm model (R2 ≥ 0.994) than the Freundlich isotherm model (R2 ≥ 0.982) supports the assumption that the monolayer adsorption played critical roles in the removal of Sr2+ using SCG biochar and PAC. The thermodynamic studies revealed that adsorption of Sr2+ onto SCG biochar and PAC was endothermic and happened spontaneously. Despite the significant inhibitory effects of DOM, SCG biochar exhibited the higher removal efficiencies of Sr2+ compared with PAC. Hence, SCG biochar could be considered as an alternative to PAC for the removal of Sr2+ from aqueous solutions.


Asunto(s)
Carbón Orgánico , Contaminantes Químicos del Agua , Adsorción , Café , Iones , Cinética , Estroncio , Contaminantes Químicos del Agua/análisis
5.
Environ Pollut ; 270: 116244, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33321433

RESUMEN

This study investigated the competitive adsorption mechanisms of pharmaceuticals (i.e., naproxen, diclofenac, and ibuprofen) toward the pristine and NaOH-activated biochars from spent coffee wastes (SCW) in lake water and wastewater effluent. The kinetic and isotherm studies revealed that the improved physicochemical characteristics and physically homogenized surfaces of the pristine SCW biochar through the chemical activation with NaOH were beneficial to the adsorption of pharmaceuticals (competitive equilibrium adsorption capacity (Qe, exp): NaOH-activated SCW biochar (61.25-192.07 µmol/g) > pristine SCW biochar (14.81-20.65 µmol/g)). The adsorptive removal of naproxen (Qe, exp = 14.81-18.81 µmol/g), diclofenac (Qe, exp = 15.73-20.00 µmol/g), and ibuprofen (Qe, exp = 16.20-20.65 µmol/g) for the pristine SCW biochar showed linear correlations with their hydrophobicity (log D at pH 7.0: ibuprofen (1.71) > diclofenac (1.37) > naproxen (0.25)). However, their Qe, exp values for the NaOH-activated SCW biochar (naproxen (176.39-192.07 µmol/g) > diclofenac (78.44-98.74 µmol/g) > ibuprofen (61.25-80.02 µmol/g)) were inversely correlated to the order of their log D values. These results suggest that the reinforced aromatic structure of the NaOH-activated SCW biochar facilitated the π-π interaction. The calculated thermodynamic parameters demonstrated that the competitive adsorption of pharmaceuticals on the NaOH-activated SCW biochar compared to pristine SCW biochar occurred more spontaneously over the entire pH (5.0-11.0) and ionic strength (NaCl: 0-0.125 M) ranges. These observations imply that the NaOH-activated SCW biochar might be potentially applicable for the removal of pharmaceuticals in lake water and wastewater effluent.


Asunto(s)
Preparaciones Farmacéuticas , Contaminantes Químicos del Agua , Adsorción , Carbón Orgánico , Café , Interacciones Hidrofóbicas e Hidrofílicas , Lagos , Hidróxido de Sodio , Aguas Residuales , Agua , Contaminantes Químicos del Agua/análisis
6.
J Hazard Mater ; 400: 123102, 2020 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-32947732

RESUMEN

This study investigated the single and competitive adsorption characteristics of micropollutants using the pristine and alkali-modified spent coffee grounds (SCG) biochars. The alkali modification substantially improved the physicochemical characteristics of the SCG biochars (specific surface area and pore volume), which may have led to differences in the adsorption behaviors of the micropollutants. The pseudo second order model (R2 ≥ 0.990) better described the single and competitive adsorption kinetics than the pseudo first order model (R2 ≥ 0.664). It is evident that chemisorption played a key role in the removal of the micropollutants by the pristine and alkali-modified SCG biochars. The single and competitive adsorptions of the micropollutants were highly dependent on the solution pH and ionic strength since the pore-filling effects, electrostatic and hydrophobic interactions governed their removal by the pristine and alkali-modified SCG biochars. The higher removal efficiencies of the micropollutants by the alkali-modified SCG biochars (≥ 44.5%) in the presence of dissolved organic matter compared to the pristine SCG biochars (≤ 18.5%) support the assumption that alkali modification could markedly reinforce the surface structural properties of the SCG biochars related to the adsorption capacities.


Asunto(s)
Álcalis , Café , Adsorción , Carbón Orgánico
7.
PLoS One ; 15(1): e0228054, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31945143

RESUMEN

PURPOSE: This qualitative study identifies difficulties and unmet needs in psychosocial aspect that Korean cancer survivors reported. MATERIALS AND METHODS: We enrolled 18 cancer survivors who agreed to participate in the focus groups. Each focus group consisted of four to six cancer survivors, considering homogeneity of sex and age. Participants were asked to freely describe the practical difficulties they faced and their unmet needs when living as cancer survivors. A cross-case interview analysis was used to identify major themes. Consensual qualitative research analysis was applied to complement the objectivity of results obtained from participants' interviews. RESULTS: We identified three major themes: 1) shifts what cancer connotes, 2) development of government policies regarding integrative management for cancer survivors, and 3) preparing for cancer survivors' future through vocational rehabilitation or career development. CONCLUSION: Korean cancer survivors had difficulties in psychosocial adjustment even after the completion of anti-cancer treatments. We identified several unmet needs among participants who were living as cancer survivors. This qualitative study may expand the view of cancer survivorship in Korea by incorporating their voices and experiences to facilitate the development of a more holistic cancer survivorship program.


Asunto(s)
Supervivientes de Cáncer/psicología , Necesidades y Demandas de Servicios de Salud , Calidad de Vida/psicología , Adulto , Anciano , Femenino , Grupos Focales , Humanos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , República de Corea
8.
Proc Natl Acad Sci U S A ; 115(16): 4282-4287, 2018 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-29610348

RESUMEN

Cigarette smoking is the leading cause of preventable disease and death in the United States, with more persons dying from nicotine addiction than any other preventable cause of death. Even though smoking cessation incurs multiple health benefits, the abstinence rate remains low with current medications. Here we show that the AMP-activated protein kinase (AMPK) pathway in the hippocampus is activated following chronic nicotine use, an effect that is rapidly reversed by nicotine withdrawal. Increasing pAMPK levels and, consequently, downstream AMPK signaling pharmacologically attenuate anxiety-like behavior following nicotine withdrawal. We show that metformin, a known AMPK activator in the periphery, reduces withdrawal symptoms through a mechanism dependent on the presence of the AMPKα subunits within the hippocampus. This study provides evidence of a direct effect of AMPK modulation on nicotine withdrawal symptoms and suggests central AMPK activation as a therapeutic target for smoking cessation.


Asunto(s)
Proteínas Quinasas Activadas por AMP/efectos de los fármacos , Trastornos de Ansiedad/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Metformina/uso terapéutico , Proteínas del Tejido Nervioso/efectos de los fármacos , Nicotina/efectos adversos , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/fisiología , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacología , Animales , Trastornos de Ansiedad/inducido químicamente , Trastornos de Ansiedad/enzimología , Evaluación Preclínica de Medicamentos , Activación Enzimática/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Hipocampo/enzimología , Masculino , Metformina/farmacología , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/fisiología , Ribonucleótidos/farmacología , Transducción de Señal/efectos de los fármacos , Síndrome de Abstinencia a Sustancias/enzimología , Tabaquismo/enzimología , Tabaquismo/psicología
9.
Int J Clin Oncol ; 23(2): 287-297, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29134362

RESUMEN

BACKGROUND: This study investigated the role of hyperthermia combined with preoperative concurrent chemoradiotherapy (CCRT) for locally advanced rectal cancer (LARC) according to hypoxic marker expression. METHODS: One hundred and nine LARC patients with tissue blocks available for immunohistochemical assessment of carbonic anhydrase 9 (CA9) expression were reviewed. CA9 expression was considered positive when the staining percentage of tumor cells was >25% (n = 31). Pelvic radiotherapy with a total dose of 39.6-45 Gy was delivered concurrently with fluorouracil-based chemotherapy. Hyperthermia was administered to 52 patients twice a week during CCRT. Treatment response and outcomes were compared between hyperthermochemoradiotherapy (HCRT) and CCRT groups. RESULTS: In patients with positive CA9 expression, the rates of downstaging (p = 0.060) and pathologic complete response (p = 0.064) tended to be higher in the HCRT group than in the CCRT group. Distant metastasis-free survival (p = 0.029) and cancer-specific survival (p = 0.020) were significantly worse in tumors with both positive CA9 expression and poor tumor response. Negative CA9 expression, presence of major tumor response, and the use of hyperthermia were significant favorable prognostic factors for cancer-specific survival after the first recurrence in multivariate analysis. CONCLUSIONS: Hyperthermia might selectively enhance the preoperative treatment response in LARC with positive CA9 expression and offset the negative effect of hypoxia on prognosis. Pretreatment evaluation of hypoxia could aid in the selection of patients who might benefit from hyperthermia.


Asunto(s)
Antígenos de Neoplasias/análisis , Anhidrasa Carbónica IX/análisis , Selección de Paciente , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Anciano , Quimioradioterapia/métodos , Terapia Combinada , Femenino , Fluorouracilo/uso terapéutico , Humanos , Hipertermia Inducida/métodos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Cuidados Preoperatorios , Pronóstico , Neoplasias del Recto/mortalidad , Tasa de Supervivencia , Insuficiencia del Tratamiento , Resultado del Tratamiento
10.
Cancer Chemother Pharmacol ; 79(6): 1161-1167, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28447209

RESUMEN

PURPOSE: We aimed to present the clinical outcomes of adjuvant concurrent chemoradiotherapy (CCRT) with low-dose daily cisplatin regimen compared to the conventional 5-fluorouracil (5-FU)-based regimen for extrahepatic bile duct cancer (EHBDC). METHODS: From October 1994 to April 2013, 41 patients received adjuvant CCRT with low-dose daily regimen or 5-FU-based regimens. Nineteen patients received low-dose of cisplatin just before every delivery of radiation therapy, and 21 patients received two cycles of 5-FU-based regimen during radiotherapy. We compared the clinical outcomes between two adjuvant CCRT regimens. RESULTS: Adjuvant CCRT with low-dose daily cisplatin showed comparable toxicity profiles compared with that of a 5-FU-based regimen. The median follow-up time was 33 months (range, 5-205), and the 5-year overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 34.2, 50.8, and 49.7%, respectively. Univariable analyses showed no significant differences in OS, LRRFS, and DMFS between the groups with two regimens. In multivariable analyses, chemotherapeutic regimen was a significant prognostic factor for OS, favoring the low-dose daily cisplatin regimen (HR = 2.491, p = 0.036) over 5-FU-based regimen, though not for LRRFS (p = 0.642) and DMFS (p = 0.756). CONCLUSIONS: Adjuvant CCRT with low-dose daily cisplatin regimen showed acceptable toxicities and survivals compared to those of the 5-FU-based regimen. Low-dose daily cisplatin can be one of the feasible regimens for adjuvant CCRT for EHBDC.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de los Conductos Biliares/terapia , Quimioradioterapia Adyuvante/métodos , Cisplatino/uso terapéutico , Adulto , Anciano , Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/radioterapia , Conductos Biliares Extrahepáticos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Terapia Combinada/efectos adversos , Comorbilidad , Femenino , Fluorouracilo/uso terapéutico , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia
11.
J Korean Med Sci ; 30(12): 1723-32, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26713046

RESUMEN

This study involved a cost-utility analysis of early diagnosis and treatment of diabetic retinopathy depending on the screening strategy used. The four screening strategies evaluated were no screening, opportunistic examination, systematic fundus photography, and systematic examination by an ophthalmologists. Each strategy was evaluated in 10,000 adults aged 40 yr with newly diagnosed diabetes mellitus (hypothetical cohort). The cost of each strategy was estimated in the perspective of both payer and health care system. The utility was estimated using quality-adjusted life years (QALY). Incremental Cost Effectiveness Ratio (ICER) for the different screening strategies was analyzed. After exclusion of the weakly dominating opportunistic strategy, the ICER of systematic photography was 57,716,867 and that of systematic examination by ophthalmologists was 419,989,046 from the perspective of the healthcare system. According to the results, the systematic strategy is preferable to the opportunistic strategy from the perspective of both a payer and a healthcare system. Although systematic examination by ophthalmologists may have higher utility than systematic photography, it is associated with higher cost. The systematic photography is the best strategy in terms of cost-utility. However systematic examination by ophthalmologists can also be a suitable policy alternative, if the incremental cost is socially acceptable.


Asunto(s)
Análisis Costo-Beneficio , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/terapia , Tamizaje Masivo/economía , Adulto , Anciano , Anciano de 80 o más Años , Retinopatía Diabética/economía , Técnicas de Diagnóstico Oftalmológico/economía , Diagnóstico Precoz , Femenino , Angiografía con Fluoresceína/economía , Costos de la Atención en Salud , Humanos , Masculino , Cadenas de Markov , Tamizaje Masivo/métodos , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Modelos Económicos , Programas Nacionales de Salud/economía , Años de Vida Ajustados por Calidad de Vida , República de Corea
12.
Biol Psychiatry ; 77(4): 345-55, 2015 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-25442004

RESUMEN

BACKGROUND: Acetylation of heat shock protein 90 (Hsp90) regulates downstream hormone signaling via the glucocorticoid receptor (GR), but the role of this molecular mechanism in stress homeostasis is poorly understood. We tested whether acetylation of Hsp90 in the brain predicts and modulates the behavioral sequelae of a mouse model of social stress. METHODS: Mice subjected to chronic social defeat stress were stratified into resilient and vulnerable subpopulations. Hypothalamic-pituitary-adrenal axis function was probed using a dexamethasone/corticotropin-releasing factor test. Measurements of Hsp90 acetylation, Hsp90-GR interactions, and GR translocation were performed in the dorsal raphe nucleus. To manipulate Hsp90 acetylation, we pharmacologically inhibited histone deacetylase 6, a known deacetylase of Hsp90, or overexpressed a point mutant that mimics the hyperacetylated state of Hsp90 at lysine K294. RESULTS: Lower acetylated Hsp90, higher GR-Hsp90 association, and enhanced GR translocation were observed in dorsal raphe nucleus of vulnerable mice after chronic social defeat stress. Administration of ACY-738, a histone deacetylase 6-selective inhibitor, led to Hsp90 hyperacetylation in brain and in neuronal culture. In cell-based assays, ACY-738 increased the relative association of Hsp90 with FK506 binding protein 51 versus FK506 binding protein 52 and inhibited hormone-induced GR translocation. This effect was replicated by overexpressing the acetylation-mimic point mutant of Hsp90. In vivo, ACY-738 promoted resilience to chronic social defeat stress, and serotonin-selective viral overexpression of the acetylation-mimic mutant of Hsp90 in raphe neurons reproduced the behavioral effect of ACY-738. CONCLUSIONS: Hyperacetylation of Hsp90 is a predictor and causal molecular determinant of stress resilience in mice. Brain-penetrant histone deacetylase 6 inhibitors increase Hsp90 acetylation and modulate GR chaperone dynamics offering a promising strategy to curtail deleterious socioaffective effects of stress and glucocorticoids.


Asunto(s)
Adaptación Psicológica/fisiología , Proteínas HSP90 de Choque Térmico/metabolismo , Histona Desacetilasas/metabolismo , Receptores de Glucocorticoides/metabolismo , Estrés Psicológico/metabolismo , Acetilación , Animales , Corticosterona/sangre , Núcleo Dorsal del Rafe/metabolismo , Histona Desacetilasa 6 , Hipotálamo/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Sistema Hipófiso-Suprarrenal/metabolismo , Transducción de Señal , Conducta Social , Estrés Psicológico/enzimología
13.
Proc Natl Acad Sci U S A ; 109(2): 616-20, 2012 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-22203993

RESUMEN

The AMP-activated kinase (AMPK) senses the energy status of cells and regulates fuel availability, whereas hypothalamic AMPK regulates food intake. We report that inositol polyphosphate multikinase (IPMK) regulates glucose signaling to AMPK in a pathway whereby glucose activates phosphorylation of IPMK at tyrosine 174 enabling the enzyme to bind to AMPK and regulate its activation. Thus, refeeding fasted mice rapidly and markedly stimulates transcriptional enhancement of IPMK expression while down-regulating AMPK. Also, AMPK is up-regulated in mice with genetic depletion of hypothalamic IPMK. IPMK physiologically binds AMPK, with binding enhanced by glucose treatment. Regulation by glucose of phospho-AMPK in hypothalamic cell lines is prevented by blocking AMPK-IPMK binding. These findings imply that IPMK inhibitors will be beneficial in treating obesity and diabetes.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Regulación de la Expresión Génica/fisiología , Glucosa/metabolismo , Hipotálamo/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Transducción de Señal/fisiología , Animales , Cromatografía Líquida de Alta Presión , Electroforesis en Gel de Poliacrilamida , Inmunoprecipitación , Ratones , Fosforilación , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Tirosina/metabolismo
14.
Proc Natl Acad Sci U S A ; 104(9): 3456-9, 2007 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-17360666

RESUMEN

The atypical antipsychotic drugs (AAPDs) have markedly enhanced the treatment of schizophrenias but their use has been hindered by the major weight gain elicited by some AAPDs. We report that orexigenic AAPDs potently and selectively activate hypothalamic AMP-kinase, an action abolished in mice with deletion of histamine H1 receptors. These findings may afford a means of developing more effective therapeutic agents and provide insight into the hypothalamic regulation of food intake.


Asunto(s)
Adenilato Quinasa/metabolismo , Antipsicóticos/efectos adversos , Hipotálamo/enzimología , Receptores Histamínicos H1/metabolismo , Aumento de Peso/efectos de los fármacos , Animales , Activación Enzimática/efectos de los fármacos , Inmunohistoquímica , Ratones , Fosforilación
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