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1.
Sci Total Environ ; 926: 172022, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38552970

RESUMEN

While combinations of pesticides better represent actual conditions within aquatic ecosystems, the specific toxic effects of these combinations have not been determined yet. The objective of this research was to assess the combined impact of imazalil and azoxystrobin on the hook snout carp (Opsariichthys bidens) and delve into the underlying causes. Our findings indicated that the 4-day LC50 value for imazalil (1.85 mg L-1) was greater than that for azoxystrobin (0.90 mg L-1). When imazalil and azoxystrobin were combined, they presented a heightened effect on the species. Enzyme activities like SOD, CAT, GST, and CarE, along with androgen and estrogen levels, displayed marked differences in most single and combined treatments in comparison to the baseline group. Moreover, four genes (mn-sod, cu-sod, il-1, and esr) related to oxidative stress, immunity, and the endocrine system exhibited more pronounced expression changes when exposed to combined pesticides rather than individual ones. Our tests revealed that the combined use of imazalil and azoxystrobin had more detrimental effect on aquatic vertebrates than when evaluated individually. This finding suggested that future ecological hazard analyses based only on individual tests might not sufficiently safeguard our aquatic ecosystems.


Asunto(s)
Carpas , Imidazoles , Plaguicidas , Pirimidinas , Estrobilurinas , Contaminantes Químicos del Agua , Animales , Ecosistema , Superóxido Dismutasa , Estrés Oxidativo , Contaminantes Químicos del Agua/toxicidad
2.
Huan Jing Ke Xue ; 44(7): 4151-4161, 2023 Jul 08.
Artículo en Chino | MEDLINE | ID: mdl-37438312

RESUMEN

In order to understand the heavy metal contamination of soil and vegetables in the vegetable production system of Zhejiang Province and the health risks of vegetables consumed by residents, typical vegetable production bases in Zhejiang Province were selected as the study areas; 102 pairs of vegetable and soil samples were collected; the distribution characteristics of heavy metals Cd, Cu, Pb, Cr, As, Ni, and Hg in the vegetable production system of Zhejiang Province were analyzed, and the ecological health risks of the vegetable production system were systematically evaluated using the Nemerow composite pollution index, potential ecological risk index, and dietary exposure assessment model. The results showed that Cd in the soil seriously exceeded the standard, with an exceedance rate of 97.2%. The main risk of soil pollution was moderate and mild, and the highest risk was Cd, followed by Pb, Cu, and As. Among vegetables, only a small amount of bean and fruit vegetables exceeded the Cd content, with the exceedance rates of 12.5% and 8.7%, respectively. The BCF of different types of vegetables differed significantly and could be ranked accordingly:leafy vegetables>bean vegetables>melon vegetables>root vegetables. The non-carcinogenic and carcinogenic risks of Zhejiang residents consuming local vegetables were within acceptable limits, with children being more at risk than adults (P<0.01), and Cd and Pb contributing the most to health risks. The overall vegetables produced by the vegetable production system in Zhejiang Province were at a safe level, but there is a need to strengthen the control of Cd and Pb pollution sources.


Asunto(s)
Metales Pesados , Verduras , Adulto , Niño , Humanos , Cadmio , Plomo , Contaminación Ambiental
3.
Toxins (Basel) ; 15(6)2023 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-37368690

RESUMEN

Wheat grains are susceptible to contamination with various natural mycotoxins including regulated and emerging mycotoxins. This study surveyed the natural presence of regulated mycotoxins, such as deoxynivalenol (DON) and zearalenone (ZEN), and emerging mycotoxins such as beauvericin (BEA), enniatins (ENNs such as ENA, ENA1, ENB, ENB1) and Alternaria mycotoxins (i.e., alternariol monomethyl ether (AME), alternariol (AOH), tenuazonic acid (TeA), tentoxin (TEN), and altenuene (ALT)) in wheat grains randomly collected from eight provinces across China in 2021. The results revealed that each wheat grain sample was detected with at least one type of mycotoxin. The detection rates of these mycotoxins ranged from 7.1% to 100%, with the average occurrence level ranging from 1.11 to 921.8 µg/kg. DON and TeA were the predominant mycotoxins with respect to both prevalence and concentration. Approximately 99.7% of samples were found to contain more than one toxin, and the co-occurrence of ten toxins (DON + ZEN + ENA + ENA1 + ENB + ENB1 + AME + AOH + TeA + TEN) was the most frequently detected combination. The dietary exposure to different mycotoxins among Chinese consumers aged 4-70 years was as follows: 0.592-0.992 µg/kg b.w./day for DON, 0.007-0.012 µg/kg b.w./day for ZEN, 0.0003-0.007 µg/kg b.w./day for BEA and ENNs, 0.223-0.373 µg/kg b.w./day for TeA, and 0.025-0.041 µg/kg b.w./day for TEN, which were lower than the health-based guidance values for each mycotoxin, with the corresponding hazard quotient (HQ) being far lower than 1, implying a tolerable health risk for Chinese consumers. However, the estimated dietary exposure to AME and AOH was in the range of 0.003-0.007 µg/kg b.w./day, exceeding the Threshold of Toxicological Concern (TTC) value of 0.0025 µg/kg b.w./day, demonstrating potential dietary risks for Chinese consumers. Therefore, developing practical control and management strategies is essential for controlling mycotoxins contamination in the agricultural systems, thereby ensuring public health.


Asunto(s)
Micotoxinas , Zearalenona , Micotoxinas/análisis , Triticum , Exposición Dietética/efectos adversos , Contaminación de Alimentos/análisis , Espectrometría de Masas en Tándem/métodos , Zearalenona/análisis , Ácido Tenuazónico/análisis , China , Alternaria
4.
Chemosphere ; 326: 138429, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36933844

RESUMEN

Despite the current efforts to identify the mixtures of chemical pollutants, they are often "binned" into their corresponding pollutant groups. Limited studies have investigated complex mixtures of chemical pollutants co-occurring across different groups. The combined toxic impacts of several substances become a critical consideration in toxicology because chemical combinations can exert a greater deleterious effect than the single components in the mixture. In the current work, we assessed the joint impacts of ochratoxin A and tricyclazole on the zebrafish (Danio rerio) embryos and explored their underlying signaling pathways. Ochratoxin A displayed higher toxicity than tricyclazole, with a 10-day LC50 of 0.16 mg L-1, whereas that for tricyclazole was 1.94 mg L-1. The combination of ochratoxin A and tricyclazole exhibited a synergistic impact on D. rerio. The activities of detoxification enzymes GST and CYP450, as well as apoptosis-associated enzyme caspase 3, were distinctly changed in most individual and mixture exposures comparing to the untreated group. Upon both individual and mixture exposures, more dramatic variations were detected in the expressions of nine genes, such as the apoptosis genes cas3 and bax, antioxidant gene mn-sod, immunosuppression gene il-1ß, and the endocrine system genes trα, dio1, trß, ugtlab, and crh, compared with the untreated group. These findings suggested that the simultaneous exposure to low doses of mycotoxins and pesticides in food commodities was more toxic than predicted from the individual chemicals. Considering the frequent co-occurrence of mycotoxins and pesticides in the diet, this synergy should be considered in future assessments.


Asunto(s)
Ocratoxinas , Plaguicidas , Contaminantes Químicos del Agua , Animales , Pez Cebra/metabolismo , Larva , Plaguicidas/toxicidad , Ocratoxinas/toxicidad , Ocratoxinas/metabolismo , Contaminantes Químicos del Agua/metabolismo , Embrión no Mamífero
5.
Sci Total Environ ; 838(Pt 4): 156296, 2022 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-35660440

RESUMEN

The soil quality benefits from switching from chisel-disk (CD) operations to continuous no-till (NT) in corn (Zea mays L.) and soybean (Glycine max L.) rotations have been proven over time; but to mitigate climate change, effects of continuous NT on nitrous oxide (N2O) emissions must be evaluated. The objectives of this study were to determine the influence of contrasting tillage practices (CD vs. NT) on soil N2O emissions, soil nitrogen (N) dynamics, corn grain yields, N removals and partial N balances, soil volumetric water content (VWC) and soil temperature following 48 and 50 years of tillage implementation in a long-term corn-soybean rotation experiment in a poorly-drained Alfisol. A four-time replicated randomized complete block design was conducted with tillage treatments [CD (grower's current practice) and NT] as main plots and fertility [a no-fertilizer control (CTR) and fertilizing corn N, P, and K (NPK)] as subplots. Corn grain yield, N removal, and partial N balances were greater in CD than NT in 2018 but not in 2020. Soil N2O-N was similar among tillage treatments in 2018 (3.2 kg N2O-N ha-1) but higher in CD (8.5 kg N2O-N ha-1) than in NT (6.2 kg N2O-N ha-1) in 2020. The CD treatment had higher two-yr cumulative N2O-N emissions (11.9 kg N2O-N ha-1) than NT (9.1 kg N2O-N ha-1), indicating that NT has a potential for reducing N2O-N in poorly-drained Alfisols. Grain yield-scaled N2O-N was lower in NT than CD in 2020 but not in 2018. Soil N2O emissions were positively associated with soil NO3-N, partial N balances, and corn grain yield and negatively associated with soil bulk density and temperature. We concluded that after 48 and 50 years, continuous NT can maintain corn grain yield and mitigate N2O-N emissions indicating to mitigate climate change and increase multi-sphere benefits, continuous NT practices should be implemented.


Asunto(s)
Óxido Nitroso , Suelo , Agricultura , Productos Agrícolas , Fertilizantes/análisis , Nitrógeno/análisis , Óxido Nitroso/análisis , Glycine max , Zea mays
6.
J Environ Manage ; 260: 110092, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-31941630

RESUMEN

China is facing serious heavy metal pollution in farmland soil, which is a major pressing concern for food safety and human health. This research delivers an integrated methodology for pollution source apportionment and a soil-rice-human model to predict heavy metal transfer in the farmland soil, rice grain and human blood chain. The source identification integrated positive matrix factorization (PMF), cluster analysis (CA) and the life cycle assessment (LCA) survey of agricultural and industrial production and consumption. Based on the case analysis of Shaoxing, this method showed very good performance through the illustration of the source contributions by PMF and LCA at county level and the identification of the pollution sources using CA and LCA at field scale. According to the overall evaluation, the integrated method was superior for the farmland metals pollution source identification comparing to existing source apportionment methods. To predict metal transformation in soil-rice-human chain, a set of models of metals (As, Pb, Cd, Hg, Cr) accumulation ability in rice grain and human blood has been established by literature review and monitoring data. The models showed adequate predictability for the metal content of rice grains at both the field and regional scale, and plausible simulation of the metal concentration in human blood throughout the whole study region. Therefore, this study provides valuable tools for farmland soil heavy metal pollution source identification and for the prediction of heavy metal transformation in soil-rice-human chain; and it can highlight the need to take mitigating action to reduce farmland metal pollution risks in specific regions.


Asunto(s)
Metales Pesados , Oryza , Contaminantes del Suelo , China , Monitoreo del Ambiente , Granjas , Humanos , Medición de Riesgo , Suelo
7.
J Hazard Mater ; 354: 161-169, 2018 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-29751172

RESUMEN

Source apportionment is a crucial step toward reduction of heavy metal pollution in soil. Existing methods are generally based on receptor models. However, overestimation or underestimation occurs when they are applied to heavy metal source apportionment in soil. Therefore, a modified model (PCA-MLRD) was developed, which is based on principal component analysis (PCA) and multiple linear regression with distance (MLRD). This model was applied to a case study conducted in a peri-urban area in southeast China where soils were contaminated by arsenic (As), cadmium (Cd), mercury (Hg) and lead (Pb). Compared with existing models, PCA-MLRD is able to identify specific sources and quantify the extent of influence for each emission. The zinc (Zn)-Pb mine was identified as the most important anthropogenic emission, which affected approximately half area for Pb and As accumulation, and approximately one third for Cd. Overall, the influence extent of the anthropogenic emissions decreased in the order of mine (3 km) > dyeing mill (2 km) ≈ industrial hub (2 km) > fluorescent factory (1.5 km) > road (0.5 km). Although algorithm still needs to improved, the PCA-MLRD model has the potential to become a useful tool for heavy metal source apportionment in soil.

8.
J Environ Manage ; 207: 159-168, 2018 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-29174991

RESUMEN

Heavy metal pollution in peri-urban areas in China is serious and complex. We thus developed an integrated evaluation method to assess heavy metal pollution and potential health risk to residents in a typical peri-urban area with diverse anthropogenic emission sources and cropping systems. Ecological risk was evaluated using Nemerow's synthetical pollution index (Pn) and Potential ecological risk index (RI). Then polluted areas and responsible emission sources were identified by GIS mapping. Health risk caused by food intake and soil exposure was calculated by accounting for the influence of anthropogenic emissions and cropping systems. Agricultural soils in the study area were polluted by cadmium (Cd), mercury (Hg), lead (Pb), and arsenic (As). High concentrations mainly occurred near the mining area and along the roadsides. The accumulation of heavy metals in crops followed the order of tea leaves > rice grain > vegetables. The hazard index of potential human health risk caused by chronic soil exposure and food intake was 15.3, indicating obvious adverse health effects. 87.5% of health risk was attributed to food consumption, and significantly varied among different cropping systems with the decreasing order of rice (10.44) >vegetable (2.86) > tea (0.05). The integrated method of ecological and health risk index, which takes consideration of both anthropogenic emission and cropping system can provide a practical tool for evaluating of agricultural soil in the peri-urban area regrading different risk factors.


Asunto(s)
Metales Pesados , Medición de Riesgo , Contaminantes del Suelo , China , Salud Ambiental , Monitoreo del Ambiente , Humanos , Suelo
9.
Environ Sci Pollut Res Int ; 24(23): 19293-19305, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28669090

RESUMEN

Phytoremediation coupled with crop rotation (PCC) is a feasible strategy for remediation of contaminated soil without interrupting crop production. The objective of this study was to develop a PCC technology system for greenhouse fields co-contaminated with Cd and nitrate using hyperaccumulator Sedum alfredii. In this system, endophytic bacterium M002 inoculation, CO2 fertilization, and fermentation residue were continuously applied to improve the growth of S. alfredii, and low-accumulator Ipomoea aquatica and low-accumulator Brassica chinensis were rotated under reasonable water management. These comprehensive management practices were shown to increase S. alfredii biomass and Cd uptake and reduce Cd and nitrate concentration in I. aquatica and B. chinensis. This crop rotating system could remove 56.5% total Cd, 62.3% DTPA extractable Cd, and 65.4% nitrate, respectively, from the co-contaminated soil in 2 years of phytoremediation, and is an effective way of remediating moderately co-contaminated soil by Cd and nitrate.


Asunto(s)
Brassica/crecimiento & desarrollo , Cadmio/análisis , Producción de Cultivos/métodos , Ipomoea/crecimiento & desarrollo , Nitratos/análisis , Sedum/crecimiento & desarrollo , Contaminantes del Suelo/análisis , Biodegradación Ambiental , Biomasa , Cadmio/metabolismo , Nitratos/metabolismo , Sedum/metabolismo , Suelo/química , Contaminantes del Suelo/metabolismo
10.
Environ Pollut ; 226: 230-239, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28377193

RESUMEN

China was considered the biggest contributor for airborne mercury in the world but the amount of mercury emission in effluents and solid wastes has not been documented. In this study, total national and regional mercury emission to the environment via exhaust gases, effluents and solid wastes were accounted with updated emission factors and the amount of goods produced and/or consumed. The national mercury emission in China increased from 448 to 2151 tons during the 1980-2012 period. Nearly all of the emissions were ended up as exhaust gases and solid wastes. The proportion of exhaust gases decreased with increasing share of solid wastes and effluents. Of all the anthropogenic sources, coal was the most important contributor in quantity, followed by mercury mining, gold smelting, nonferrous smelting, iron steel production, domestic wastes, and cement production, with accounting for more than 90% of the total emission. There was a big variation of regional cumulative mercury emission during 1980-2012 in China, with higher emissions occurred in eastern areas and lower values in the western and far northern regions. The biggest cumulative emission occurred in GZ (Guizhou), reaching 3974 t, while the smallest cumulative emission was lower than 10 t in XZ (Tibet). Correspondingly, mercury accumulation in soil were higher in regions with larger emissions in unit area. Therefore, it is urgent to reduce anthropogenic mercury emission and subsequent impact on ecological functions and human health.


Asunto(s)
Contaminantes Atmosféricos/análisis , Contaminación del Aire/estadística & datos numéricos , Monitoreo del Ambiente , Mercurio/análisis , China , Carbón Mineral/análisis , Humanos , Hierro , Minería , Suelo , Tibet
11.
J Hazard Mater ; 299: 540-9, 2015 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-26257294

RESUMEN

Three techniques (Isotope Ratio Analysis, GIS mapping, and Multivariate Statistical Analysis) were integrated to assess heavy metal pollution and source apportionment in peri-urban agricultural soils. The soils in the study area were moderately polluted with cadmium (Cd) and mercury (Hg), lightly polluted with lead (Pb), and chromium (Cr). GIS Mapping suggested Cd pollution originates from point sources, whereas Hg, Pb, Cr could be traced back to both point and non-point sources. Principal component analysis (PCA) indicated aluminum (Al), manganese (Mn), nickel (Ni) were mainly inherited from natural sources, while Hg, Pb, and Cd were associated with two different kinds of anthropogenic sources. Cluster analysis (CA) further identified fertilizers, waste water, industrial solid wastes, road dust, and atmospheric deposition as potential sources. Based on isotope ratio analysis (IRA) organic fertilizers and road dusts accounted for 74-100% and 0-24% of the total Hg input, while road dusts and solid wastes contributed for 0-80% and 19-100% of the Pb input. This study provides a reliable approach for heavy metal source apportionment in this particular peri-urban area, with a clear potential for future application in other regions.

12.
Sci Total Environ ; 512-513: 659-671, 2015 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-25668202

RESUMEN

Manure nitrogen (N) in the livestock sector has become a key driver of environmental change. The denitrification-decomposition (DNDC) model was used to evaluate N pollution strengths on Andosols with intensive dairy manure application in Upper Naka River Watershed, Japan. The calibrated model was capable of predicting Andosol N flows because the simulated soil mineral N content, soil nitrogen oxide (N2O) fluxes, denitrification rate, and crop N uptake matched the patterns and magnitudes of the field observations from a wide range of soil textures, as well as manure management and cropping systems. The simulations showed that current intensive manure application systems caused low crop N use efficiency and a large amount of NO3(-)-N leaching and N2O emission. The crop N use efficiency was 27%-42% and 37%-55% of input N for uplands and paddy rice, respectively. The uplands showed much more serious N environmental pollution risks with N leaching 123-362 kg N ha(-1) yr(-1) and N2O emissions 6.53-11.8 kg N ha(-1) yr(-1) than that in the lowland paddy rice with N leaching 17.4-103 kg N ha(-1) yr(-1) and N2O emissions 0.59-2.77 kg N ha(-1) yr(-1). Forage rice/barley crop systems have high N cleaning capability due to the greater crop N uptake which reached to 304 kg N ha(-1) yr(-1). High precipitation stimulated more NO3(-)-N leaching. Sandy soil also showed higher N leaching and was unsuitable for paddy rice. Slurry application stimulated more N2O emission than compost manure. To mitigate the current high N pollution, the critical N application rate was recommended to be approximately 380, 470, 640, and 390 kg N ha(-1) yr(-1) for loam sand planted with maize/grass, loam soil with maize/grass, forage rice/barley, and rice/fallow with winter manure application, respectively.


Asunto(s)
Industria Lechera , Monitoreo del Ambiente , Modelos Químicos , Contaminantes del Suelo/análisis , Suelo/química , Japón , Nitrógeno/análisis
13.
Neurobiol Aging ; 33(4): 732-43, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20674096

RESUMEN

Previous studies identified engulfment adapter phosphotyrosine binding (PTB) domain containing 1 (GULP1) as an NPXY-motif interactor of low-density lipoprotein receptor-related protein 1 (LRP1) and suggested a potential relevance in Alzheimer's disease (AD). Since AD associated proteins amyloid-ß A4 precursor protein (APP) and LRP1 were shown to interact with the PTB domain of Fe65 and several other adapters via their intracellular NPXY-motifs, we examined a possible interaction of GULP1 PTB domain with the YENPTY-motif of APP. Here we demonstrate that GULP1 is present in human hippocampal and neocortical neurons. Confocal live cell imaging revealed that coexpressed and endogenous GULP1 colocalizes with APP in the Golgi and endoplasmic reticulum. Analysis of the interacting domains by co-immunoprecipitation of point and deletion mutants revealed that the interaction depends on the PTB domain of GULP1 and the YENPTY-motif of APP. Coexpression of GULP1 affected APP cell surface localization and suppressed generation of Aß40/42 and sAPPα. Taken together, these data identify GULP1 as a novel neuronal APP interacting protein that alters trafficking and processing of APP.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Regulación de la Expresión Génica/fisiología , Neuronas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Secuencias de Aminoácidos/genética , Secretasas de la Proteína Precursora del Amiloide/genética , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animales , Ácido Aspártico Endopeptidasas/genética , Ácido Aspártico Endopeptidasas/metabolismo , Biotinilación , Células Cultivadas , Embrión de Mamíferos , Retículo Endoplásmico/metabolismo , Regulación de la Expresión Génica/genética , Aparato de Golgi/metabolismo , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Hipocampo/citología , Humanos , Inmunoprecipitación , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Ratones , Microscopía Confocal , Neocórtex/citología , Neuronas/ultraestructura , Fragmentos de Péptidos/metabolismo , Transporte de Proteínas/genética , Transporte de Proteínas/fisiología , Transfección
14.
Neurosci Lett ; 442(2): 91-5, 2008 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-18602448

RESUMEN

The ability of the low density lipoprotein receptor-related protein (LRP) to form homo-dimers was studied in mouse neuroblastoma and human neuroglioma cells as well as in primary cortical cultures from adult mouse brain. Homo-dimerization of LRP light chain (LC) was shown by several methods including co-immunoprecipitation, fluorescence lifetime imaging microscopy, and bimolecular fluorescence complementation assay. The requirement of intact NPXY motifs of LRP LC for homo-dimerization was ruled out by co-immunoprecipitation assay.


Asunto(s)
Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Neuronas/metabolismo , Homología de Secuencia de Aminoácido , Secuencias de Aminoácidos , Animales , Células Cultivadas , Corteza Cerebral/citología , Embrión de Mamíferos , Endocitosis , Transferencia Resonante de Energía de Fluorescencia/métodos , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Ratones , Procesamiento Proteico-Postraduccional , Transfección/métodos
15.
J Neurosci ; 26(39): 9913-22, 2006 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-17005855

RESUMEN

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.


Asunto(s)
Factores de Ribosilacion-ADP/fisiología , Proteínas Adaptadoras del Transporte Vesicular/fisiología , Precursor de Proteína beta-Amiloide/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Animales , Ácido Aspártico Endopeptidasas/metabolismo , Química Encefálica , Línea Celular , Línea Celular Tumoral , Transferencia Resonante de Energía de Fluorescencia , Glicosilación , Aparato de Golgi/metabolismo , Humanos , Riñón/citología , Riñón/embriología , Ratones , Neuroblastoma/patología , Fragmentos de Péptidos/metabolismo , Procesamiento Proteico-Postraduccional , Estructura Terciaria de Proteína , Transporte de Proteínas/fisiología , Proteínas Recombinantes de Fusión/metabolismo , Eliminación de Secuencia , Relación Estructura-Actividad , Transfección
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