8 research outputs found

    The Lysosomal v-ATPase-Ragulator Complex Is a Common Activator for AMPK and mTORC1, Acting as a Switch between Catabolism and Anabolism

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    林圣彩教授课题组长期致力于细胞信号转导的研究。近年来,该课题组潜心研究,不断攻关,取得了一系列重大成果,如揭示细胞如何应对生长因子缺乏的内在机理,发现了细胞自噬“路线图”、还发现了细胞如何感应“饥饿”信号AMP的信号传导通路等。其中,“发现细胞自噬‘路线图’”成果曾登上《科学》杂志,并入选2012年度“中国科学十大进展”。AMPK and mTOR play principal roles in governing metabolic programs; however, mechanisms underlying the coordination of the two inversely regulated kinases remain unclear. In this study we found, most surprisingly, that the late endosomal/lysosomal protein complex v-ATPase-Ragulator, essential for activation of mTORC1, is also required for AMPK activation. We also uncovered that AMPK is a residential protein of late endosome/lysosome. Under glucose starvation, the v-ATPase-Ragulator complex is accessible to AXIN/LKB1 for AMPK activation. Concurrently, the guanine nucleotide exchange factor (GEF) activity of Ragulator toward RAG is inhibited by AXIN, causing dissociation from endosome and inactivation of mTORC1. We have thus revealed that the v-ATPase-Ragulator complex is also an initiating sensor for energy stress and meanwhile serves as an endosomal docking site for LKB1-mediated AMPK activation by forming the v-ATPase-Ragulator-AXIN/LKB1-AMPK complex, thereby providing a switch between catabolism and anabolism. Our current study also emphasizes a general role of late endosome/lysosome in controlling metabolic programs

    Use of nanomaterials in the pretreatment of water samples for environmental analysis

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    The challenge of providing clean drinking water is of enormous relevance in today’s human civilization, being essential for human consumption, but also for agriculture, livestock and several industrial applications. In addition to remediation strategies, the accurate monitoring of pollutants in water sup-plies, which most of the times are present at low concentrations, is a critical challenge. The usual low concentration of target analytes, the presence of in-terferents and the incompatibility of the sample matrix with instrumental techniques and detectors are the main reasons that renders sample preparation a relevant part of environmental monitoring strategies. The discovery and ap-plication of new nanomaterials allowed improvements on the pretreatment of water samples, with benefits in terms of speed, reliability and sensitivity in analysis. In this chapter, the use of nanomaterials in solid-phase extraction (SPE) protocols for water samples pretreatment for environmental monitoring is addressed. The most used nanomaterials, including metallic nanoparticles, metal organic frameworks, molecularly imprinted polymers, carbon-based nanomaterials, silica-based nanoparticles and nanocomposites are described, and their applications and advantages overviewed. Main gaps are identified and new directions on the field are suggested.publishe

    Comparative Assessment of the Antioxidant Activities among the Extracts of Different Parts of Clausena lansium (Lour.) Skeels in Human Gingival Fibroblast Cells

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    Clausena lansium (Lour.) Skeels (wampee) is an outstanding natural plant with medicinal properties. The aim of this study was to compare the cytoprotective effects of four parts of wampee under oxidative stress. The aqueous extracts of leaf, peel, pulp, and seed were tested for the proliferation effects on human gingival fibroblast (HGF) cells and the protective effects in the hydrogen peroxide-induced HGF model. Furthermore, the total glutathione assay and identification of rutin by high-performance liquid chromatography were carried out to attempt to determine whether the cytoprotective effects were related to the total glutathione (GSH) stability and rutin content. The results showed that all of the extracts had no cytotoxicity to HGF at tested concentrations ranging from 50 to 5000 μg/ml during 24 h, and the leaf, pulp, and seed extracts increased proliferation of HGF at relatively high concentrations. All the extracts except for the seed extract significantly decreased the production of reactive oxygen species, and the peel extracts exhibited the most effective antioxidant effect. The leaf extract had the highest anticytotoxicity and GSH stabilization effect in the HGF challenged with hydrogen peroxide. In addition, the relative content of rutin in peel and leaf extracts was higher than that in pulp and seed. The results of GSH assay and rutin identification suggest that different cellular protective effects among the four parts of wampee are partially related to the GSH stabilization and rutin content. These findings provide a scientific basis for the antioxidant effect-related biological activities of wampee extracts
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