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1.
ACS Appl Mater Interfaces ; 16(15): 18855-18866, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38577763

RESUMEN

Solar-driven interfacial evaporation provides a promising pathway for sustainable freshwater and energy generation. However, developing highly efficient photothermal and photocatalytic nanomaterials is challenging. Herein, substoichiometric molybdenum oxide (MoO3-x) nanoparticles are synthesized via step-by-step reduction treatment of l-cysteine under mild conditions for simultaneous photothermal conversion and photocatalytic reactions. The MoO3-x nanoparticles of low reduction degree are decorated on hydrophilic cotton cloth to prepare a MCML evaporator toward rapid water production, pollutant degradation, as well as electricity generation. The obtained MCML evaporator has a strong local light-to-heat effect, which can be attributed to excellent photothermal conversion via the local surface plasmon resonance effect in MoO3-x nanoparticles and the low heat loss of the evaporator. Meanwhile, the rich surface area of MoO3-x nanoparticles and the localized photothermal effect together effectively accelerate the photocatalytic degradation reaction of the antibiotic tetracycline. With the benefit of these advantages, the MCML evaporator attains a superior evaporation rate of 4.14 kg m-2 h-1, admirable conversion efficiency of 90.7%, and adequate degradation efficiency of 96.2% under 1 sun irradiation. Furthermore, after being rationally assembled with a thermoelectric module, the hybrid device can be employed to generate 1.0 W m-2 of electric power density. This work presents an effective complementary strategy for freshwater production and sewage treatment as well as electricity generation in remote and off-grid regions.

2.
Nat Commun ; 14(1): 8461, 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38123537

RESUMEN

Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) play crucial roles in supporting hematopoiesis and hematopoietic regeneration. However, whether ECs are a source of BMSCs remains unclear. Here, we evaluate the contribution of endothelial-to-mesenchymal transition to BMSC generation in postnatal mice. Single-cell RNA sequencing identifies ECs expressing BMSC markers Prrx1 and Lepr; however, this could not be validated using Prrx1-Cre and Lepr-Cre transgenic mice. Additionally, only a minority of BMSCs are marked by EC lineage tracing models using Cdh5-rtTA-tetO-Cre or Tek-CreERT2. Moreover, Cdh5+ BMSCs and Tek+ BMSCs show distinct spatial distributions and characteristic mesenchymal markers, suggestive of their origination from different progenitors rather than CDH5+ TEK+ ECs. Furthermore, myeloablation induced by 5-fluorouracil treatment does not increase Cdh5+ BMSCs. Our findings indicate that ECs hardly convert to BMSCs during homeostasis and myeloablation-induced hematopoietic regeneration, highlighting the importance of using appropriate genetic models and conducting careful data interpretation in studies concerning endothelial-to-mesenchymal transition.


Asunto(s)
Células Endoteliales , Células Madre Mesenquimatosas , Ratones , Animales , Médula Ósea , Ratones Transgénicos
3.
Mater Today Bio ; 23: 100854, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38024846

RESUMEN

Bone regeneration heavily relies on bone marrow mesenchymal stem cells (BMSCs). However, recruiting endogenous BMSCs for in situ bone regeneration remains challenging. In this study, we developed a novel BMSC-aptamer (BMSC-apt) functionalized hydrogel (BMSC-aptgel) and evaluated its functions in recruiting BMSCs and promoting bone regeneration. The functional hydrogels were synthesized between maleimide-terminated 4-arm polyethylene glycols (PEG) and thiol-flanked PEG crosslinker, allowing rapid in situ gel formation. The aldehyde group-modified BMSC-apt was covalently bonded to a thiol-flanked PEG crosslinker to produce high-density aptamer coverage on the hydrogel surface. In vitro and in vivo studies demonstrated that the BMSC-aptgel significantly increased BMSC recruitment, migration, osteogenic differentiation, and biocompatibility. In vivo fluorescence tomography imaging demonstrated that functionalized hydrogels effectively recruited DiR-labeled BMSCs at the fracture site. Consequently, a mouse femur fracture model significantly enhanced new bone formation and mineralization. The aggregated BMSCs stimulated bone regeneration by balancing osteogenic and osteoclastic activities and reduced the local inflammatory response via paracrine effects. This study's findings suggest that the BMSC-aptgel can be a promising and effective strategy for promoting in situ bone regeneration.

4.
Inflamm Res ; 72(10-11): 2053-2072, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37816881

RESUMEN

OBJECTIVE: Nanoparticles (NPs) hold a great promise in combating rheumatoid arthritis, but are often compromised by their toxicities because the currently used NPs are usually synthesized by chemical methods. Our group has previously fabricated Ångstrom-scale silver particles (AgÅPs) and demonstrated the anti-tumor and anti-sepsis efficacy of fructose-coated AgÅPs (F-AgÅPs). This study aimed to uncover the efficacy and mechanisms of F-AgÅPs for arthritis therapy. METHODS: We evaluated the efficacy of F-AgÅPs in collagen-induced arthritis (CIA) mice. We also compared the capacities of F-AgÅPs, the commercial AgNPs, and the clinical drug methotrexate (MTX) in protecting against K/BxN serum-transfer arthritis (STA) mice. Moreover, we evaluated the effects of F-AgÅPs and AgNPs on inflammation, osteoclast formation, synoviocytes migration, and matrix metalloproteinases (MMPs) production in vitro and in vivo. Meanwhile, the toxicities of F-AgÅPs and AgNPs in vitro and in vivo were also tested. RESULTS: F-AgÅPs significantly prevented bone erosion, synovitis, and cartilage damage, attenuated rheumatic pain, and improved the impaired motor function in mouse models of CIA or STA, the anti-rheumatic effects of which were comparable or stronger than AgNPs and MTX. Further studies revealed that F-AgÅPs exhibited similar or greater inhibitory abilities than AgNPs to suppress inflammation, osteoclast formation, synoviocytes migration, and MMPs production. No obvious toxicities were observed in vitro and in vivo after F-AgÅPs treatment. CONCLUSIONS: F-AgÅPs can effectively alleviate arthritis without notable toxicities and their anti-arthritic effects are associated with the inhibition of inflammation, osteoclastogenesis, synoviocytes migration, and MMPs production. Our study suggests the prospect of F-AgÅPs as an efficient and low-toxicity agent for arthritis therapy.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Ratones , Animales , Plata/uso terapéutico , Osteogénesis , Inflamación/tratamiento farmacológico , Inflamación/patología , Artritis Reumatoide/tratamiento farmacológico , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Colágeno , Metotrexato/farmacología , Metotrexato/uso terapéutico , Metaloproteinasas de la Matriz
5.
ChemSusChem ; 16(2): e202201935, 2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36441157

RESUMEN

Converting poly(ethylene terephthalate) (PET) into metal-organic frameworks (MOFs) has emerged as a promising innovation for upcycling of waste plastics. However, previous solvothermal methods suffer from toxic solvent consumption, long reaction time, high pressure, and high temperature. Herein, a mechanochemical milling strategy was reported to transform waste PET into a series of MOFs with high yields. This strategy had the merits of solvent-free conditions, ambient reaction temperature, short running time, and easy scale-up for large-scale production of MOFs. The as-prepared MOFs exhibited definite crystal structure and porous morphology composed of agglomerated nanoparticles. It was proven that, under mechanochemical milling, PET was firstly decomposed into 1,4-benzenedicarboxylate, which acted as linkers to coordinate with metal ions for forming fragments, followed by the gradual arrangement of fragments into MOFs. This work not only promotes high value-added conversion of waste polyesters but also offers a new opportunity to produce MOFs in a green and scalable manner.

6.
ACS Appl Mater Interfaces ; 14(40): 45533-45544, 2022 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-36178300

RESUMEN

The integration of renewable solar energy-driven interfacial evaporation and photocatalysis has recently emerged as one of the most promising technologies for simultaneous freshwater production and pollutant removal. However, the construction of an advanced integrated system with the merit of a fast supply of water and pollutant molecules remains challenging for efficient solar-driven evaporation and photocatalytic performance. Herein, inspired by the transpiration of plants, we fabricate a biomimetic, vertically channeled polypyrrole/foam-like carbon nitride/poly(vinyl alcohol) hydrogel (PCH) by directional freeze-drying. We prove that the vertically aligned channels not only reduce heat loss and improve energy conversion efficiency but also facilitate the transport of water and organic pollutants to the air-water interface. Benefiting from the advantages above, the PCH evaporator presents a high solar evaporation efficiency of 92.5%, with the evaporation rate achieving 2.27 kg m-2 h-1 under 1 kW m-2 irradiation, exceeding many advanced interfacial solar-driven evaporators. Meanwhile, PCH reaches a degradation efficiency of 90.6% within 1 h when dealing with tetracycline (a typical antibiotic)-polluted water, remarkably higher than that of the hydrogel without vertically aligned channels (68.6%). Furthermore, the as-formed reactive oxygen species effectively kill Gram-positive and Gram-negative bacterial in the source water, achieving the all-round water purification. In an outdoor experiment, after 11 h of sunlight irradiation, the tetracycline degradation efficiency and freshwater production of the PCH evaporator rise to 99.0% and 6.2 kg m-2, respectively. This work highlights the novel biomimetic approach to fabricate multifunctional photothermal materials for simultaneous freshwater production and polluted-water remediation.


Asunto(s)
Contaminantes Ambientales , Purificación del Agua , Antibacterianos , Biomimética , Hidrogeles , Polímeros , Alcohol Polivinílico , Pirroles , Especies Reactivas de Oxígeno , Tetraciclinas , Agua
7.
J Mater Chem B ; 10(28): 5454-5464, 2022 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-35786741

RESUMEN

The SARS-CoV-2 pandemic has become a severe global public health event, and the development of protective and therapeutic strategies is urgently needed. Downregulation of angiotensin converting enzyme 2 (ACE2; one of the important SARS-CoV-2 entry receptors) and aberrant inflammatory responses (cytokine storm) are the main targets to inhibit and control COVID-19 invasion. Silver nanomaterials have well-known pharmaceutical properties, including antiviral, antibacterial, and anticancer properties. Here, based on a self-established metal evaporation-condensation-size graded collection system, smaller silver particles reaching the Ångstrom scale (AgÅPs) were fabricated and coated with fructose to obtain a stabilized AgÅP solution (F-AgÅPs). F-AgÅPs potently inactivated SARS-CoV-2 and prevented viral infection. Considering the application of anti-SARS-CoV-2, a sterilized F-AgÅP solution was produced via spray formulation. In our model, the F-AgÅP spray downregulated ACE2 expression and attenuated proinflammatory factors. Moreover, F-AgÅPs were found to be rapidly eliminated to avoid respiratory and systemic toxicity in this study as well as our previous studies. This work presents a safe and potent anti-SARS-CoV-2 agent using an F-AgÅP spray.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , Tratamiento Farmacológico de COVID-19 , Humanos , Peptidil-Dipeptidasa A/metabolismo , SARS-CoV-2 , Plata/farmacología
8.
Nat Commun ; 13(1): 1453, 2022 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-35304471

RESUMEN

Adipocyte differentiation of bone marrow mesenchymal stem/stromal cells (BMSCs) instead of osteoblast formation contributes to age- and menopause-related marrow adiposity and osteoporosis. Vascular calcification often occurs with osteoporosis, a contradictory association called "calcification paradox". Here we show that extracellular vesicles derived from aged bone matrix (AB-EVs) during bone resorption favor BMSC adipogenesis rather than osteogenesis and augment calcification of vascular smooth muscle cells. Intravenous or intramedullary injection of AB-EVs promotes bone-fat imbalance and exacerbates Vitamin D3 (VD3)-induced vascular calcification in young or old mice. Alendronate (ALE), a bone resorption inhibitor, down-regulates AB-EVs release and attenuates aging- and ovariectomy-induced bone-fat imbalance. In the VD3-treated aged mice, ALE suppresses the ovariectomy-induced aggravation of vascular calcification. MiR-483-5p and miR-2861 are enriched in AB-EVs and essential for the AB-EVs-induced bone-fat imbalance and exacerbation of vascular calcification. Our study uncovers the role of AB-EVs as a messenger for calcification paradox by transferring miR-483-5p and miR-2861.


Asunto(s)
Vesículas Extracelulares , Células Madre Mesenquimatosas , MicroARNs , Animales , Matriz Ósea , Diferenciación Celular , Femenino , Ratones , MicroARNs/genética , Osteogénesis
9.
J Cardiothorac Surg ; 16(1): 327, 2021 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-34749774

RESUMEN

BACKGROUND: CircMMP11 is a characterized circRNA with oncogenic function in breast cancer. In this study, we explored the involvement of circMMP11 in non-small cell lung cancer (NSCLC). METHODS: Paired cancer and non-cancer tissues were collected from 66 NSCLC patients, and the expression of circMMP11 and miR-143 in these tissues were detected using RT-qPCRs. Overexpression levels of circMMP11 and miR-143 were performed by transfection, and their crosstalk was analyzed by RT-qPCRs. The effect of circMMP11 overexpression on miR-143 methylation was analyzed by methylation-specific PCR. CCK-8 assay was performed to analyze the roles of miR-143 and circMMP11 in regulating NSCLC cell proliferation. RESULTS: We found that circMMP11 was overexpressed in NSCLC and predicted patients' poor survival. Moreover, a close correlation between circMMP11 and miR143 was observed. In NSCLC cells, circMMP11 overexpression reduced miR-143 expression and increased miR-143 methylation. CCK-8 assay analysis showed that miR-143 reversed the enhancing effects of circMMP11 overexpression on cell proliferation. CONCLUSIONS: CircMMP11 is overexpressed in NSCLC and predicts poor survival. In addition, circMMP11 may downregulate miR-143 through methylation to suppress cell proliferation.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , ARN Complementario/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Proliferación Celular , Humanos , Neoplasias Pulmonares/genética , Metilación , MicroARNs/genética , MicroARNs/metabolismo
10.
Aging Med (Milton) ; 1(1): 64-66, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31942482

RESUMEN

Chronic noncommunicable diseases (NCDs) are the leading cause of death, accounting for 70% of global deaths. Also referred to as chronic diseases, NCDs mainly include cardiovascular disease (such as heart disease and stroke), cancer, chronic respiratory disease (such as chronic obstructive pulmonary disease and asthma), and diabetes. The incidence of NCDs is rising over time, becoming one of the most important threats to human health. As a measurement of quality of life, scales can reflect the entire health status of patients. But there are still many disadvantages in the multidimensional health status of elderly patients with chronic diseases, so it is of great significance to develop a simple and practical multidimensional health scale of good reliability and validity for chronic diseases in the elderly.

11.
Brain Inj ; 31(12): 1651-1655, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28898108

RESUMEN

BACKGROUND: A large cranial defect combined with hydrocephalus is a frequent sequela of decompressive craniectomy (DC) performed to treat malignant intracranial hypertension. Currently, many neurosurgeons perform simultaneous cranioplasty and shunt implantation on such patients, but the safety of this combined procedure remains controversial. METHODS: We retrospectively evaluated 58 patients treated via cranioplasty and shunt implantation after DC. Twenty patients underwent simultaneous procedures (simultaneous operation group) and 38 underwent staged procedures (staged operation group). We collected and analysed demographic data, information on disease histories, and clinical findings. RESULTS: The overall complication rate was 19%. The two groups did not significantly differ regarding the all-complication (30% vs. 13%), bleeding complication (0% vs. 5%), or treatment failure (15% vs. 3%) rates. However, the rate of surgical site infection/incision healing problems (25% vs. 3%) and the re-operation rate (20% vs. 3%) were significantly higher in the simultaneous operation group. CONCLUSION: Patients undergoing simultaneous cranioplasty/shunt implantation may be at a higher risk of infectious complications than those undergoing staged operations.


Asunto(s)
Craniectomía Descompresiva/métodos , Hipertensión Intracraneal/cirugía , Derivación Ventriculoperitoneal/métodos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Derivación Ventriculoperitoneal/instrumentación
12.
Brain Inj ; 29(13-14): 1654-60, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26513495

RESUMEN

BACKGROUND: A large cranial defect following decompressive craniectomy (DC) is a common sequela in patients with severe traumatic brain injury (TBI). Such a defect can cause severe disturbance of cerebral blood flow (CBF) regulation. This study investigated the impact of cranioplasty on CBF in these patients. METHODS: Patients who underwent DC and secondary cranioplasty were prospectively studied for a severe TBI. CT perfusion was used to measure CBF before and after cranioplasty. The basal ganglia, parietal lobe and occipital lobe on the decompressed side were chosen as zones of interest for CBF evaluation. RESULTS: Nine patients representing nine cranioplasty procedures were included in the study. Before cranioplasty, CBF on the decompressed side was lower than that on the contralateral side. During the early stage (10 days) after cranioplasty, CBF on the decompressed side was increased and this increase was significant in the parietal and occipital lobe. CBF was also increased on the contralateral side. In addition, the difference in CBF between the contralateral side and the decompressed side was reduced after cranioplasty. Further, the CT perfusion showed that the CBFs decreased again 3 months post-cranioplasty among four cases, but was still higher than those before cranioplasty. CONCLUSIONS: This study indicates that cranioplasty may increase CBF and benefit the recovery in patients with DC for TBI.


Asunto(s)
Lesiones Encefálicas/fisiopatología , Lesiones Encefálicas/cirugía , Circulación Cerebrovascular/fisiología , Craniectomía Descompresiva/métodos , Adulto , Femenino , Escala de Consecuencias de Glasgow , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Procedimientos de Cirugía Plástica/métodos , Cráneo/cirugía , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
13.
J Colloid Interface Sci ; 445: 195-204, 2015 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-25618239

RESUMEN

Novel porous cup-stacked carbon nanotube (P-CSCNT) with special stacked morphology consisting of many truncated conical graphene layers was synthesized by KOH activating CSCNT from polypropylene. The morphology, microstructure, textural property, phase structure, surface element composition and thermal stability of P-CSCNT were investigated by field-emission scanning electron microscope, transmission electron microscope (TEM), high-resolution TEM, N2 sorption, X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy and thermal gravimetric analysis. A part of oblique graphitic layers were etched by KOH, and many holes with a diameter of several to a doze of nanometers connecting inner tube with outside were formed, which endowed P-CSCNT with high specific surface area (558.7 m(2)/g), large pore volume (1.993 cm(3)/g) and abundant surface functional groups. Subsequently, P-CSCNT was used for adsorption of methylene blue (MB) from wastewater. Langmuir model closely fitted the adsorption results, and the maximum adsorption capacity of P-CSCNT was as high as 319.1mg/g. This was ascribed to multiple adsorption mechanisms including pore filling, hydrogen bonding, π-π and electrostatic interactions. Pseudo second-order kinetic model was more valid to describe the adsorption behavior. Besides, P-CSCNT showed good recyclablity and reusability. These results demonstrated that P-CSCNT had potential application in wastewater treatment.

14.
Environ Sci Technol ; 48(7): 4048-55, 2014 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-24611910

RESUMEN

The catalytic carbonization of polyolefin materials to synthesize carbon nanotubes (CNTs) is a promising strategy for the processing and recycling of plastic wastes, but this approach is generally limited due to the selectivity of catalysts and the difficulties in separating the polyolefin mixture. In this study, the influence of nanosized carbon black (CB) and Ni2O3 as a novel combined catalyst system on catalyzing carbonization of polypropylene (PP), polyethylene (PE), polystyrene (PS) and their blends was investigated. We showed that this combination was efficient to promote the carbonization of these polymers to produce CNTs with high yields and of good quality. Catalytic pyrolysis and model carbonization experiments indicated that the carbonization mechanism was attributed to the synergistic effect of the combined catalysts rendered by CB and Ni2O3: CB catalyzed the degradation of PP, PE, and PS to selectively produce more aromatic compounds, which were subsequently dehydrogenated and reassembled into CNTs via the catalytic action of CB together with Ni particles. Moreover, the performance of the synthesized CNTs as the electrode of supercapacitor was investigated. The supercapacitor displayed a high specific capacitance as compared to supercapacitors using commercial CNTs and CB. This difference was attributed to the relatively larger specific surface areas of our synthetic CNTs and their more oxygen-containing groups.


Asunto(s)
Capacidad Eléctrica , Nanotubos de Carbono/química , Níquel/química , Óxidos/química , Tamaño de la Partícula , Polienos/química , Hollín/química , Residuos/análisis , Adsorción , Catálisis , Electrodos , Modelos Teóricos , Nanotubos de Carbono/ultraestructura , Polietileno/química , Poliestirenos/química , Espectrometría Raman , Temperatura , Difracción de Rayos X
15.
Plant Cell Rep ; 31(12): 2215-27, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22926030

RESUMEN

KEY MESSAGE: Overexpressing TaUb2 promoted stem growth and resulted in early flowering in transgenic tobacco plants. Ubiquitin are involved in the production, metabolism and proper function of gibberellin. The ubiquitin-26S proteasome system (UPS), in which ubiquitin (Ub) functions as a marker, is a post-translational regulatory system that plays a prominent role in various biological processes. To investigate the impact of different Ub levels on plant growth and development, transgenic tobacco (Nicotiana tabacum L.) plants were engineered to express an Ub gene (TaUb2) from wheat (Triticum aestivum L.) under the control of cauliflower mosaic virus 35S promoter. Transgenic tobacco plants overexpressing TaUb2 demonstrated an accelerated growth rate at early stage and an early flowering phenotype in development. The preceding expression of MADS-box genes also corresponded to the accelerated developmental phenotypes of the transgenic tobacco plants compared to that of wild-type (WT). Total gibberellin (GA) and active GA contents in transgenic tobacco plants were higher than those in WT at the corresponding developmental stages, and some GA metabolism genes were upregulated. Treatment with GA(3) conferred a similarly accelerated grown rate in WT plants to that of transgenic tobacco plants, while growth was inhibited when transgenic tobacco plants were treated with a GA biosynthesis inhibitor. Thus, the results suggest that Ub are involved in the production, metabolism and proper function of GA, which is important in the regulation of plant growth and development.


Asunto(s)
Giberelinas/metabolismo , Nicotiana/metabolismo , Triticum/genética , Ubiquitina/metabolismo , Caulimovirus/genética , Flores/efectos de los fármacos , Flores/genética , Flores/crecimiento & desarrollo , Flores/metabolismo , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Fenotipo , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Tallos de la Planta/efectos de los fármacos , Tallos de la Planta/genética , Tallos de la Planta/crecimiento & desarrollo , Tallos de la Planta/metabolismo , Plantas Modificadas Genéticamente/efectos de los fármacos , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Plantas Modificadas Genéticamente/metabolismo , Regiones Promotoras Genéticas , Factores de Tiempo , Nicotiana/efectos de los fármacos , Nicotiana/genética , Nicotiana/crecimiento & desarrollo , Triazoles/farmacología , Ubiquitina/genética
16.
J Neurosci Res ; 87(11): 2498-508, 2009 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-19326444

RESUMEN

We determined the molecular mechanisms underlying apolipoprotein E (ApoE)-isoform-dependent lipid efflux from neurons and ApoE-deficient astrocytes in culture. The ability of ApoE3 to induce lipid efflux was 2.5- to 3.9-fold greater than ApoE4. To explore the contributions of the amino- and carboxyl-terminal tertiary structure domains of ApoE to cellular lipid efflux, each domain was studied separately. The amino-terminal fragment of ApoE3 (22-kDa-ApoE3) induced lipid efflux greater than 22-kDa-ApoE4, whereas the common carboxyl-terminal fragment of ApoE induced very low levels of lipid efflux. Addition of segments of the carboxyl-terminal domain to 22-kDa-ApoE3 additively induced lipid efflux in a length-dependent manner; in contrast, this effect did not occur with ApoE4. This observation, coupled with the fact that introduction of the E255A mutation (which disrupts domain-domain interaction) into ApoE4 increases lipid efflux, indicates that interaction between the amino- and carboxyl-terminal domains in ApoE4 reduces the ability of this isoform to mediate lipid efflux from neural cells. Dimeric 22-kDa or intact ApoE3 induced higher lipid efflux than monomeric 22-kDa or intact ApoE3, respectively, indicating that dimerization of ApoE3 enhances the ability to release lipids. The adenosine triphosphate-binding cassette protein A1 (ABCA1) is involved in ApoE-induced lipid efflux. In conclusion, there are two major factors, intramolecular domain interaction and intermolecular dimerization, that cause ApoE-isoform-dependent lipid efflux from neural cells in culture.


Asunto(s)
Apolipoproteína E3/metabolismo , Apolipoproteína E4/metabolismo , Astrocitos/metabolismo , Colesterol/metabolismo , Neuronas/metabolismo , Fosfatidilcolinas/metabolismo , Transportador 1 de Casete de Unión a ATP , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Animales , Apolipoproteína E3/genética , Apolipoproteína E4/genética , Astrocitos/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Células Cultivadas , Fármacos del Sistema Nervioso Central/farmacología , Gliburida/farmacología , Humanos , Hidroxicolesteroles/farmacología , Mutación , Neuronas/efectos de los fármacos , Multimerización de Proteína/fisiología , Ratas , Factores de Tiempo
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