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1.
Membranes (Basel) ; 12(11)2022 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-36422133

RESUMEN

Reverse electrodialysis (RED) power generation using seawater (SW) and river water is expected to be a promising environmentally friendly power generation system. Experiments with large RED stacks are needed for the practical application of RED power generation, but only a few experimental results exist because of the need for large facilities and a large area of ion-exchange membranes (IEMs). In this study, to predict the power output of a large RED stack, the power generation performances of a lab-scale RED stack (40 membrane pairs and 7040 cm2 total effective membrane area) with several IEMs were evaluated. The results were converted to the power output of a pilot-scale RED stack (299 membrane pairs and 179.4 m2 total effective membrane area) via the reference IEMs. The use of low-area-resistance IEMs resulted in lower internal resistance and higher power density. The power density was 2.3 times higher than that of the reference IEMs when natural SW was used. The net power output was expected to be approximately 230 W with a pilot-scale RED stack using low-area-resistance IEMs and natural SW. This value is one of the indicators of the output of a large RED stack and is a target to be exceeded with further improvements in the RED system.

2.
Membranes (Basel) ; 12(2)2022 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-35207104

RESUMEN

This study compared the performance of two microbial fuel cells (MFCs) equipped with separators of anion or cation exchange membranes (AEMs or CEMs) for sewage wastewater treatment. Under chemostat feeding of sewage wastewater (hydraulic retention time of approximately 7 h and polarization via an external resistance of 1 Ω), the MFCs with AEM (MFCAEM) generated a maximum current that was 4-5 times greater than that generated by the MFC with CEM (MFCCEM). The high current in the MFCAEM was attributed to the approximately neutral pH of its cathode, in contrast to the extremely high pH of the MFCCEM cathode. Due to the elimination of the pH imbalance, the cathode resistance for the MFCAEM (13-19 Ω·m2) was lower than that for the MFCCEM (41-44 Ω·m2). The membrane resistance measured as the Cl- mobility of AEMs for the MFCAEM operated for 35, 583, and 768 days showed an increase with operation time and depth, and this increase contributed minimally to the cathode resistance of the MFCAEM. These results indicate the advantage of the AEM over the CEM for air-cathode MFCs. The membrane resistance may increase when the AEM is applied in large-scale MFCs on a meter scale for extended periods.

3.
Environ Res ; 205: 112416, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-34808126

RESUMEN

Although the treatment of municipal wastewater using microbial fuel cells (MFCs) has been extensively studied, scaling the systems up for practical use remains challenging. In this study, a 226 L sewage treatment reactor was equipped with 27 MFC units, and its chemical oxygen demand (COD) removal and electricity production were evaluated. The MFC units were tubular air cores with a diameter of 5 cm and length of 100 cm, which were wrapped with a carbon-based cathode, anion exchange membrane (AEM), and nonwoven graphite fabric. The air-cathode-AEM MFC generated 0.12-0.30 A/m2, 0.072-0.51 W/m3, and 1.7-4.6 Wh/m3 in a chemostat reactor with a COD of 140-36 mg/L and hydraulic retention time (HRT) of 9-42 h throughout a year. The decrease in the COD was represented as the first-order rate constant of 0.038. The rate constant was comparable to that of other air-cathode MFCs with cation exchange membranes, indicating the necessity of a posttreatment to meet the discharge standard. It has been estimated that the MFC operation for 24 h before post-aeration can reduce the energy required to meet the discharge standard by 70%, suggesting the potential applicability of MFC in long HRT-treatments such as oxidation ditch. The resistances of the anode, cathode, and AEM were 15, 7.0, and 0.51 mΩ m2, respectively, and surface dirt rather than deterioration primarily increased the AEM resistance. A current exceeding 0.2 A/m2 significantly increases the anode potential, indicating that the current was limited by low COD. Increasing the anode-specific surface area can improve air-AEM MFCs used for practical applications.


Asunto(s)
Fuentes de Energía Bioeléctrica , Purificación del Agua , Aniones , Electricidad , Electrodos , Aguas Residuales
4.
Membranes (Basel) ; 11(6)2021 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-34205395

RESUMEN

Membrane resistance and permselectivity for counter-ions have important roles in determining the performance of cation-exchange membranes (CEMs). In this study, PVA-based polyanions-poly(vinyl alcohol-b-sodium styrene sulfonate)-were synthesized, changing the molar percentages CCEG of the cation-exchange groups with respect to the vinyl alcohol groups. From the block copolymer, poly(vinyl alcohol) (PVA)-based CEMs, hereafter called "B-CEMs", were prepared by crosslinking the PVA chains with glutaraldehyde (GA) solution at various GA concentrations CGA. The ionic transport properties of the B-CEMs were compared with those previously reported for the CEMs prepared using a random copolymer-poly(vinyl alcohol-co-2-acrylamido-2-methylpropane sulfonic acid)-hereafter called "R-CEMs". The B-CEMs had lower water content than the R-CEMs at equal molar percentages of the cation-exchange groups. The charge density of the B-CEMs increased as CCEG increased, and reached a maximum value, which increased with increasing CGA. A maximum charge density of 1.47 mol/dm3 was obtained for a B-CEM with CCEG = 2.9 mol% and CGA = 0.10 vol.%, indicating that the B-CEM had almost two-thirds of the permselectivity of a commercial CEM (CMX: ASTOM Corp. Japan). The dynamic transport number and membrane resistance of a B-CEM with CCEG = 8.3 mol% and CGA = 0.10 vol.% were 0.99 and 1.6 Ωcm2, respectively. The B-CEM showed higher dynamic transport numbers than those of the R-CEMs with similar membrane resistances.

5.
Membranes (Basel) ; 11(3)2021 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-33671075

RESUMEN

Pressure-retarded osmosis (PRO) has recently received attention because of its ability to generate power via an osmotic pressure gradient between two solutions with different salinities: high- and low-salinity water sources. In this study, PRO performance, using the two pilot-scale PRO membrane modules with different configurations-five-inch cellulose triacetate hollow-fiber membrane module (CTA-HF) and eight-inch polyamide spiral-wound membrane modules (PA-SW)-was evaluated by changing the draw solution (DS) concentration, applied hydrostatic pressure difference, and the flow rates of DS and feed solution (FS), to obtain the optimum operating conditions in PRO configuration. The maximum power density per unit membrane area of PA-SW at 0.6 M NaCl was 1.40 W/m2 and 2.03-fold higher than that of CTA-HF, due to the higher water permeability coefficient of PA-SW. In contrast, the maximum power density per unit volume of CTA-SW at 0.6 M NaCl was 4.67 kW/m3 and 6.87-fold higher than that of PA-SW. The value of CTA-HF increased to 13.61 kW/m3 at 1.2 M NaCl and was 12.0-fold higher than that of PA-SW because of the higher packing density of CTA-HF.

6.
Membranes (Basel) ; 11(1)2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33401447

RESUMEN

Reverse electrodialysis (RED) is a promising process for harvesting energy from the salinity gradient between two solutions without environmental impacts. Seawater (SW) and river water (RW) are considered the main RED feed solutions because of their good availability. In Okinawa Island (Japan), SW desalination via the reverse osmosis (RO) can be integrated with the RED process due to the production of a large amount of RO brine (concentrated SW, containing ~1 mol/dm3 of NaCl), which is usually discharged directly into the sea. In this study, a pilot-scale RED stack, with 299 cell pairs and 179.4 m2 of effective membrane area, was installed in the SW desalination plant. For the first time, asymmetric monovalent selective membranes with monovalent selective layer just at the side of the membranes were used as the ion exchange membranes (IEMs) inside the RED stack. Natural and model RO brines, as well as SW, were used as the high-concentrate feed solutions. RW, which was in fact surface water in this study and close to the desalination plant, was utilized as the low-concentrate feed solution. The power generation performance investigated by the current-voltage (I-V) test showed the maximum gross power density of 0.96 and 1.46 W/m2 respectively, when the natural and model RO brine/RW were used. These are a 50-60% improvement of the maximum gross power of 0.62 and 0.97 W/m2 generated from the natural and model SW, respectively. The approximate 50% more power generated from the model feed solutions can be assigned to the suppression of concentration polarization of the RED stack due to the absence of multivalent ions.

7.
Membranes (Basel) ; 10(11)2020 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-33207567

RESUMEN

An alkali treatment under various operating conditions is conducted on a commercial anion-exchange membrane containing poly(vinyl chloride) (PVC) as a backing and binder to study the effect of the treatment on the mechanical properties by both Müllen burst and tensile tests. Contrary to our expectations, the Müllen burst pressure and tensile strain at break improved significantly after the alkali treatment in comparison to the pristine membrane and then decreased as the treatment period progressed. A good correlation is observed between the area below the stress-strain curve and burst pressure. To understand the obtained results, the PVC degradates are recovered by Soxhlet extraction and characterized via nuclear magnetic resonance and gel permeation chromatography. It is discovered that the PVC main chains degraded in the alkali solution. We propose a composite model to explain the burst pressure improvement mechanism by the change in the chemical structure of the PVC binder.

8.
Membranes (Basel) ; 10(9)2020 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-32932857

RESUMEN

Systematic alkali immersion tests of cation-exchange membranes (CEM) with polyvinyl chloride (PVC) as their backing and binder were conducted to compare that of an Anion-exchange membrane (AEM) with the same PVC materials to investigate the mechanism of dehydrochlorination. In the immersion tests, originally colorless and transparent AEM turned violet, and chemical structure analysis showed that polyene was produced by the dehydrochlorination reaction. However, the CEM did not change in color, chemical structure or membrane properties during the test with less than 1M alkali solutions. According to the Donnan equilibrium theory and the experiments using CEM and AEM, the hydroxide ion concentration in the CEM was much lower than that in the AEM under the same conditions. However, when the alkali immersion test was performed using the CEM under more severe conditions (6 M for 168 h at 40 °C), there was a slight change in the color and chemical structure of the CEM, clearly indicating that not only AEMs, but also CEMs with PVC matrixes were deteriorated by alkali, depending on the conditions.

9.
Membranes (Basel) ; 9(6)2019 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-31216734

RESUMEN

Membrane-based reverse electrodialysis (RED) can convert the salinity gradient energy between two solutions into electric power without any environmental impact. Regarding the practical application of the RED process using natural seawater and river water, the RED performance depends on the climate (temperature). In this study, we have evaluated the effect of the feed solution temperature on the resulting RED performance using two types of pilot-scale RED stacks consisting of 200 cell pairs having a total effective membrane area of 40 m2 with different intermediate distances (200 µm and 600 µm). The temperature dependence of the resistance of the solution compartment and membrane, open circuit voltage (OCV), maximum gross power output, pumping energy, and subsequent net power output of the system was individually evaluated. Increasing the temperature shows a positive influence on all the factors studied, and interesting linear relationships were obtained in all the cases, which allowed us to provide simple empirical equations to predict the resulting performance. Furthermore, the temperature dependence was strongly affected by the experimental conditions, such as the flow rate and type of stack, especially in the case of the pilot-scale stack.

10.
Membranes (Basel) ; 9(1)2019 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-30609692

RESUMEN

Hollow fiber type cation-exchange (C-HF) membranes and hollow fiber type anion-exchange (A-HF) membranes were prepared from poly (vinyl alcohol) (PVA)-based copolymer with cation-exchange groups and by blending PVA and polycation, respectively, by a gel fiber spinning method. In order to control the water content of the hollow fiber membranes, the membranes were cross-linked physically by annealing, and then cross-linked chemically by using glutaraldehyde (GA) solutions at various GA concentrations. The outer diameter of C-HF and A-HF membranes were ca. 1000 µm and ca. 1500 µm, respectively, and the thickness of the membranes were ca. 170 µm and 290 µm, respectively. Permeation experiments were carried out in two Donnan dialysis systems, which included mixed 0.1 M NaCl and 0.1 M CaCl2/C-HF /3 × 10-4 M CaCl2 and mixed 0.1 M NaCl and 0.1 M NaNO3/A-HF/3 × 10-4 M NaNO3 to examine ionic perm selectivity of the membranes. In the Donnan dialysis experiments using C-HF membranes, uphill transport of the divalent cations occurred, and, in the case of A-HF membranes, uphill transport of NO3- ions occurred. C-HF and A-HF membranes had about half of the flux in the uphill transported ions and also about half of the selectivity between the uphill transport ions and driven ions in comparison with those of the commercial flat sheet cation-exchange membrane (Neosepta® CMX) and anion-exchange membrane (Neosepta® AMX). Yet, IEC of C-HF and A-HF membranes were about one fifth of CMX and less than half of AMX, respectively. Since hollow fiber membrane module will have higher packing density than a flat membrane stack, the hollow fiber type ion-exchange membranes (IEMs) prepared in this study will have a potential application to a Donnan dialysis process.

11.
Membranes (Basel) ; 8(4)2018 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-30558251

RESUMEN

Performance of anion exchange membranes (AEMs), including polyvinyl chloride (PVC) as backing and binder, decreases during a repetitive cleaning-in-place (CIP) treatment using alkali. In this study, we have systematically performed two optical analyses, relative total visible (VIS) reflectance and handheld X-ray fluorescence (XRF), for alkali-attacked commercially available AEM (Neosepta® AMX, Tokyo, Japan) with different NaOH immersion conditions (0⁻1.0 M NaOH at 40⁻80 °C for 0⁻168 h). The VIS reflectance and XRF data were then compared with the electrical and mechanical performances (i.e., membrane resistance, proton rejection, amount of fixed-charge sites, and Young's modulus) of the alkali-attacked AMXs. The result indicated that there are clear linear relationships between their performances and both VIS reflectance and XRF data especially at 40 °C, indicating both optical analyses have a good possibility as a quick diagnosis-in-place (DIP) to predict the resulting performance of the alkali-attacked AMXs. In addition, we also found a clear linear relationship between VIS reflectance and XRF data, so that polyene formations through dehydrochlorination of PVC during alkali attack is one of dominant mechanisms for the performance reduction of the alkali-attacked AMX at 40 °C. These results are promising to be useful for the analysis of ion exchange membranes (IEMs) used in real commercial processes on-site in future.

12.
Langmuir ; 34(43): 13035-13040, 2018 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-30293431

RESUMEN

Poly(vinyl alcohol) (PVA)-based ion-exchange nanofibers (IEX-NFs) and their composite polyelectrolyte membranes were prepared and characterized. The PVA-based NFs are well dispersed and form a three-dimensional network structure in the polymer matrix, Nafion. All of the prepared membranes show a similar ion-exchange capacity of ∼1.0 mmol g-1. The ionic conductivities through the PVA- b-PSS-NF/Nafion composite membranes are superior to that of the Nafion membranes, but the conductivity through the PVA-NF/Nafion composite membrane is half that of the Nafion membrane. Our electrokinetic measurements clearly indicate that a high density of ion-exchange groups on the NF surface results in a continuous ionic transport path in the polymer matrix. In addition, the mechanical strength of all of the NF-composite membranes is improved compared with that of the membranes without NF.

13.
Membranes (Basel) ; 8(2)2018 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-29723953

RESUMEN

In this study, pressure-retarded osmosis (PRO) performance of a 5-inch scale cellulose triacetate (CTA)-based hollow fiber (HF) membrane module was evaluated under a wide range of operating conditions (0.0⁻6.0 MPa of applied pressure, 0.5⁻2.0 L/min feed solution (FS) inlet flow rate, 1.0⁻6.0 L/min DS inlet flow rate and 0.1⁻0.9 M draw solution (DS) concentration) by using a PRO/reverse osmosis (RO) hybrid system. The subsequent RO system for DS regeneration enabled the evaluation of the steady-stated module performance. In the case of pilot-scale module operation, since the DS dilution and the feed solution (FS) up-concentration had occurred and was not negligible, unlike the lab-scale experiment, PRO performance strongly depended on operating conditions such as inlet flow rates of both the DS and FS concentration. To compare the module performance with different configurations, we proposed a converted parameter in which a difference of the packing density between the spiral wound (SW) and the HF module was fairly considered. In the case of HF configuration, because of high packing density, volumetric-based performance was higher than that of SW module, that is, the required number of the module would be less than that of SW module in a full-scale PRO plant.

14.
FEBS J ; 285(5): 965-976, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29323787

RESUMEN

Transcription-coupled nucleotide excision repair (TC-NER) is a subpathway of nucleotide excision repair that efficiently removes transcription-blocking DNA damage from the transcribed strands of active genes. UVSSA is a causative gene for UV-sensitive syndrome (UVS S), which is an autosomal recessive disorder characterized by hypersensitivity to UV light and deficiency in TC-NER. UV-stimulated scaffold protein A (UVSSA), the product of UVSSA, forms a complex with ubiquitin-specific peptidase 7 (USP7) and is stabilized by interaction with USP7. The central region of UVSSA, which contains the tumor necrosis factor receptor-associated factor (TRAF)-binding motif, is required for the interaction with the N-terminal TRAF domain of USP7. Here, we showed that UVSSA is mono-ubiquitinated in vitro and identified a lysine residue (Lys414 ) in UVSSA as the target of ubiquitination. The deubiquitination activity of USP7 was inhibited by the ubiquitin-conjugating enzyme UbcH6. Lys414 was also modified by poly-ubiquitin chains in vivo. UVSSA deficient in the interaction with USP7 is ubiquitinated and degraded by the proteasome, and the degradation leads to deficiency in TC-NER. The substitution of Lys414 by Arg of UVSSA inhibited its degradation and thereby suppressed the deficiency in TC-NER.


Asunto(s)
Proteínas Portadoras/metabolismo , Reparación del ADN , Peptidasa Específica de Ubiquitina 7/metabolismo , Secuencia de Aminoácidos , Proteínas Portadoras/química , Humanos , Lisina/química , Mutación , Mutación Missense , Fenotipo , Mutación Puntual , Complejo de la Endopetidasa Proteasomal/metabolismo , Dominios y Motivos de Interacción de Proteínas , Procesamiento Proteico-Postraduccional , Proteolisis , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Factores de Transcripción/metabolismo , Péptidos y Proteínas Asociados a Receptores de Factores de Necrosis Tumoral/metabolismo , Enzimas Ubiquitina-Conjugadoras/metabolismo , Enzimas Ubiquitina-Conjugadoras/farmacología , Peptidasa Específica de Ubiquitina 7/antagonistas & inhibidores , Ubiquitinación
15.
Proc Natl Acad Sci U S A ; 115(6): E1214-E1220, 2018 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-29358370

RESUMEN

Adenine-thymine (AT)-rich interactive domain 5a (Arid5a) is an RNA-binding protein found in the cytoplasm and nucleus of normally growing cells. Although Arid5a is known to play an important role in immune regulation, whether and how Arid5a subcellular localization impacts immune regulation has remained unclear. In this study, we generated Arid5a transgenic (TG) mice to address this question. While ectopic Arid5a overexpression did not affect expression of inflammatory cytokines under unstimulated conditions, significantly higher levels of inflammatory cytokines, such as IL-6, were produced in response to lipopolysaccharide (LPS) stimulation. Consistent with this, TG mice were more sensitive to LPS treatment than wild-type mice. We also found that Arid5a is imported into the nucleus via a classical importin-α/ß1-mediated pathway. On stimulation, nuclear Arid5a levels were decreased, while there was a concomitant increase in cytoplasmic Arid5a. Arid5a is associated with up-frameshift protein 1, and its nuclear export is regulated by a nuclear export receptor, chromosomal region maintenance 1. Taken together, these data indicate that Arid5a is a dynamic protein that translocates to the cytoplasm from the nucleus so as to properly exert its dual function in mRNA stabilization and transcriptional regulation during inflammatory conditions.


Asunto(s)
Núcleo Celular/metabolismo , Citocinas/metabolismo , Citoplasma/metabolismo , Proteínas de Unión al ADN/fisiología , Inflamación/inmunología , Ribonucleasas/metabolismo , Factores de Transcripción/fisiología , Transporte Activo de Núcleo Celular , Animales , Femenino , Células HeLa , Humanos , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Lipopolisacáridos/farmacología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Fracciones Subcelulares
16.
Eur J Immunol ; 48(4): 593-604, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29244194

RESUMEN

AT-rich interactive domain-containing protein 5a (Arid5a) is an RNA-binding protein (RBP) required for autoimmunity via stabilization of interleukin-6 (Il6) and signal transducer and activator of transcription 3 (STAT3) mRNAs. However, the roles of Arid5a in Th17 cells and its association with autoimmunity remain unknown. Here, we show that the levels of Arid5a and OX40 are correlated in CD4+ T cells under Th17 conditions in an IL-6-dependent manner. Lack of Arid5a in T cells reduced OX40 expression levels and repressed IL-17 production in response to OX40 ligation. Arid5a stabilized OX40 mRNA by recognizing the alternative decay element (ADE)-like stem-loop (SL) in the 3' untranslated region (3'UTR). Interestingly, Arid5a impaired the RNA-destabilizing functions of Regnase-1 and Roquin-1 on OX40 ADE-like SL. In EAE, Arid5a-deficient mice exhibited resistance to EAE, with reduced OX40 expression in CD4+ T cells, and the number of CD4+ CD45+ T cells was decreased in CNS. Furthermore, ameliorated EAE was induced by adoptive transfer of Arid5a-/- encephalitogenic CD4+ T cells expressing less OX40 mRNA and producing less IL-17. In conclusion, our findings indicate that the Arid5a/OX40 axis in CD4+ T cells may have important implications in pathogenesis of autoimmune diseases such as EAE.


Asunto(s)
Autoinmunidad/inmunología , Proteínas de Unión al ADN/metabolismo , Glicoproteínas de Membrana/genética , Factor de Transcripción STAT3/inmunología , Células Th17/inmunología , Factores de Transcripción/metabolismo , Factores de Necrosis Tumoral/genética , Traslado Adoptivo , Animales , Autoinmunidad/genética , Línea Celular , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/patología , Células HEK293 , Humanos , Interleucina-17/biosíntesis , Interleucina-6/inmunología , Secuencias Invertidas Repetidas/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ligando OX40 , Interferencia de ARN , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Proteínas de Unión al ARN/metabolismo , Ribonucleasas/genética , Factor de Transcripción STAT3/genética , Ubiquitina-Proteína Ligasas/genética
17.
Nucleic Acids Res ; 45(5): 2687-2703, 2017 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-28168301

RESUMEN

The AT-rich interactive domain-containing protein 5a (Arid5a) plays a critical role in autoimmunity by regulating the half-life of Interleukin-6 (IL-6) mRNA. However, the signaling pathways underlying Arid5a-mediated regulation of IL-6 mRNA stability are largely uncharacterized. Here, we found that during the early phase of lipopolysaccharide (LPS) stimulation, NF-κB and an NF-κB-triggered IL-6-positive feedback loop activate Arid5a gene expression, increasing IL-6 expression via stabilization of the IL-6 mRNA. Subsequently, mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) promotes translocation of AU-rich element RNA-binding protein 1 (AUF-1) from the nucleus to the cytoplasm, where it destabilizes Arid5a mRNA by binding to AU-rich elements in the 3΄ UTR. This results in downregulation of IL-6 mRNA expression. During the late phase of LPS stimulation, p38 MAPK phosphorylates Arid5a and recruits the WW domain containing E3 ubiquitin protein ligase 1 (WWP1) to its complex, which in turn ubiquitinates Arid5a in a K48-linked manner, leading to its degradation. Inhibition of Arid5a phosphorylation and degradation increases production of IL-6 mRNA. Thus, our data demonstrate that LPS-induced NF-κB and MAPK signaling are required to control the regulation of the IL-6 mRNA stabilizing molecule Arid5a. This study therefore substantially increases our understanding of the mechanisms by which IL-6 is regulated.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Interleucina-6/genética , Sistema de Señalización de MAP Quinasas , FN-kappa B/metabolismo , Estabilidad del ARN , Receptor Toll-Like 4/metabolismo , Factores de Transcripción/metabolismo , Regiones no Traducidas 3' , Animales , Células Cultivadas , Proteínas de Unión al ADN/biosíntesis , Proteínas de Unión al ADN/genética , Fosfatasa 1 de Especificidad Dual/metabolismo , Ribonucleoproteína Nuclear Heterogénea D0 , Ribonucleoproteína Heterogénea-Nuclear Grupo D/metabolismo , Interleucina-6/metabolismo , Ratones , Ratones Endogámicos C57BL , ARN Mensajero/metabolismo , Factor de Transcripción STAT3/metabolismo , Factores de Transcripción/biosíntesis , Factores de Transcripción/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación , Regulación hacia Arriba , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
18.
Proc Natl Acad Sci U S A ; 113(41): 11543-11548, 2016 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-27671645

RESUMEN

Adenine-thymine (AT)-rich interactive domain containing protein 5a (Arid5a) is an RNA-binding protein that has been shown to play an important immune regulatory function via the stabilization of IL-6 and STAT3 mRNA. However, the role of Arid5a in the overwhelming and uncontrolled immune response that leads to septic shock is unknown. Here, we report that Arid5a-deficient mice are highly resistant to lipopolysaccharide (LPS)-induced endotoxic shock and secrete lower levels of major proinflammatory cytokines, including IFN-γ, IL-6, and TNF-α, than WT mice in response to LPS. Arid5a deficiency resulted in decreased levels of IFN-γ under Th1 cell conditions, in which T-box expressed in T cells (T-bet) mRNA expression was inhibited. Arid5a bound to the conserved stem loop structure of the 3'UTR of T-bet and stabilized its mRNA. Arid5a-deficient mice were also resistant to Propionibacterium acnes-primed LPS injection, which is considered to be a T-cell-mediated IFN-γ dependent endotoxic shock mouse model. Thus, regulation of IFN-γ by Arid5a via the stabilization of T-bet mRNA in Th1 cells contributes to the development of septic shock in mice. In addition, our previous study suggests that Arid5a control the IL-6 level in vivo in response to LPS by stabilization of IL-6 mRNA. We also observed that neutralization of IFN-γ and IL-6 significantly recovered the mice from endotoxic shock. Taken together, we conclude that Arid5a regulates the augmentation of IL-6 and IFN-γ in response to LPS, which possibly works synergistically for amplification of various other cytokines that ultimately cause the development of septic shock in mice.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Progresión de la Enfermedad , Interferón gamma/metabolismo , Estabilidad del ARN/genética , Choque Séptico/metabolismo , Proteínas de Dominio T Box/genética , Factores de Transcripción/metabolismo , Regiones no Traducidas 3'/genética , Animales , Secuencia de Bases , Separación Celular , Secuencia Conservada/genética , Citocinas/sangre , Proteínas de Unión al ADN/deficiencia , Femenino , Células HEK293 , Humanos , Lipopolisacáridos , Activación de Linfocitos , Ratones Endogámicos C57BL , Pruebas de Neutralización , Conformación de Ácido Nucleico , Propionibacterium acnes/fisiología , Unión Proteica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Choque Séptico/sangre , Choque Séptico/inmunología , Choque Séptico/microbiología , Proteínas de Dominio T Box/metabolismo , Células TH1/inmunología , Factores de Transcripción/deficiencia
19.
J Biol Chem ; 291(26): 13771-9, 2016 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-27129218

RESUMEN

UV-sensitive syndrome is an autosomal recessive disorder characterized by hypersensitivity to UV light and deficiency in transcription-coupled nucleotide excision repair (TC-NER), a subpathway of nucleotide excision repair that rapidly removes transcription-blocking DNA damage. UV-sensitive syndrome consists of three genetic complementation groups caused by mutations in the CSA, CSB, and UVSSA genes. UV-stimulated scaffold protein A (UVSSA), the product of UVSSA, which is required for stabilization of Cockayne syndrome group B (CSB) protein and reappearance of the hypophosphorylated form of RNA polymerase II after UV irradiation, forms a complex with ubiquitin-specific peptidase 7 (USP7). In this study, we demonstrated that the deubiquitination activity of USP7 is suppressed by its interaction with UVSSA. The interaction required the tumor necrosis factor receptor-associated factor domain of USP7 and the central region of UVSSA and was disrupted by an amino acid substitution in the tumor necrosis factor receptor-associated factor-binding motif of UVSSA. Cells expressing mutant UVSSA were highly sensitive to UV irradiation and defective in recovery of RNA synthesis after UV irradiation. These results indicate that the interaction between UVSSA and USP7 is important for TC-NER. Furthermore, the mutant UVSSA was rapidly degraded by the proteasome, and CSB was also degraded after UV irradiation as observed in UVSSA-deficient cells. Thus, stabilization of UVSSA by interaction with USP7 is essential for TC-NER.


Asunto(s)
Proteínas Portadoras/metabolismo , Reparación del ADN/fisiología , ARN Polimerasa II/metabolismo , Transcripción Genética/fisiología , Ubiquitina Tiolesterasa/metabolismo , Secuencias de Aminoácidos , Animales , Proteínas Portadoras/genética , Reparación del ADN/efectos de la radiación , Humanos , Estabilidad Proteica/efectos de la radiación , ARN Polimerasa II/genética , Células Sf9 , Spodoptera , Ubiquitina Tiolesterasa/genética , Peptidasa Específica de Ubiquitina 7 , Rayos Ultravioleta
20.
J Exp Med ; 213(4): 605-19, 2016 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-27022145

RESUMEN

Balance in signal transducer and activator of transcription (STAT) activation is a key factor in regulating the fate of naive CD4(+)T cells. Here, we demonstrate that AT-rich interactive domain-containing protein 5a (Arid5a) in T cells directs naive CD4(+)T cells to differentiate into inflammatory CD4(+)T cells, especially Th17 cells, through selective stabilization of Stat3(but not Stat1 and Stat5) mRNA in an IL-6-dependent manner. Loss of Arid5a in T cells led to reduction of STAT3 level under Th17-polarizing conditions, whereas STAT1 and STAT5 in Arid5a-deficient T cells were highly activated compared with those of WT T cells under the same conditions. These cells displayed the feature of antiinflammatory (Il10-expressing) CD4(+)T cells. Thus, we show a T cell-intrinsic role of Arid5a on fate decisions of naive CD4(+)T cells through selective stabilization of Stat3 mRNA.


Asunto(s)
Proteínas de Unión al ADN/inmunología , Estabilidad del ARN/inmunología , ARN Mensajero/inmunología , Factor de Transcripción STAT3/inmunología , Células Th17/inmunología , Factores de Transcripción/inmunología , Animales , Proteínas de Unión al ADN/genética , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Ratones , Ratones Noqueados , Estabilidad del ARN/genética , ARN Mensajero/genética , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/inmunología , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT5/genética , Factor de Transcripción STAT5/inmunología , Células Th17/citología , Factores de Transcripción/genética
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