6 research outputs found
KLHL1/MRP2 Mediates Neurite Outgrowth in a Glycogen Synthase Kinase 3β-Dependent Manner
The actin-based cytoskeleton is essential for the generation and maintenance of cell polarity, cellular motility, and the formation of neural cell processes. MRP2 is an actin-binding protein of the kelch-related protein family. While MRP2 has been shown to be expressed specifically in brain, its function is still unknown. Here, we report that in neuronal growth factor (NGF)-induced PC12 cells, MRP2 was expressed along the neurite processes and colocalized with Talin at the growth cones. MRP2 mRNA and protein levels were up-regulated in PC12 cells following NGF stimulation. Moreover, treatment of PC12 cells with interfering RNAs for MRP2 and glycogen synthase kinase 3β (GSK3β) resulted in the inhibition of neurite outgrowth. A significant decrease in MRP2 expression levels was observed following GSK3β inhibition, which was correlated with the inhibited neurite outgrowth, while GSK3β overexpression was found to increase MRP2 expression levels. MRP2 interacted with GSK3β through its NH(2) terminus containing the BTB domain, and these molecules colocalized along neurite processes and growth cones in differentiated PC12 cells and rat primary hippocampal neurons. Additionally, increased associations of MRP2 with GSK3β and MRP2 with actin were observed in the NGF-treated PC12 cells. Thus, this study provides, for the first time, insights into the involvement of MRP2 in neurite outgrowth, which occurs in a GSK3β-dependent manner
Catalytic synthesis of benzimidazole derivatives over modified forms of zirconia
1465-1470The solid acid catalysts, ZrO2, Mo(VI)/ZrO2 and Pt-SO42-/ZrO2 have been prepared and characterized for their surface area by BET, total surface acidity by NH3-TPD/ n-butyl amine back titration and crystallinity by powder XRD methods. These solid acid catalysts have been used in the synthesis of various benzimidazole derivatives. The results have been interpreted based on the variation of acidic properties and powder XRD phases of zirconia on incorporation of Mo(VI) or Pt-SO42– ions. Mo(VI)/ZrO2 is found to be an efficient solid acid catalyst for the synthesis of benzimidazoles with up to ~98% yield. These solid acids were found to be reusable up to at least 5 reaction cycles. Plausible mechanism for the formation of benzimidazoles over protonic acid sites of the solid acid catalysts is proposed
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Glioblastoma remodelling of human neural circuits decreases survival.
Gliomas synaptically integrate into neural circuits1,2. Previous research has demonstrated bidirectional interactions between neurons and glioma cells, with neuronal activity driving glioma growth1-4 and gliomas increasing neuronal excitability2,5-8. Here we sought to determine how glioma-induced neuronal changes influence neural circuits underlying cognition and whether these interactions influence patient survival. Using intracranial brain recordings during lexical retrieval language tasks in awake humans together with site-specific tumour tissue biopsies and cell biology experiments, we find that gliomas remodel functional neural circuitry such that task-relevant neural responses activate tumour-infiltrated cortex well beyond the cortical regions that are normally recruited in the healthy brain. Site-directed biopsies from regions within the tumour that exhibit high functional connectivity between the tumour and the rest of the brain are enriched for a glioblastoma subpopulation that exhibits a distinct synaptogenic and neuronotrophic phenotype. Tumour cells from functionally connected regions secrete the synaptogenic factor thrombospondin-1, which contributes to the differential neuron-glioma interactions observed in functionally connected tumour regions compared with tumour regions with less functional connectivity. Pharmacological inhibition of thrombospondin-1 using the FDA-approved drug gabapentin decreases glioblastoma proliferation. The degree of functional connectivity between glioblastoma and the normal brain negatively affects both patient survival and performance in language tasks. These data demonstrate that high-grade gliomas functionally remodel neural circuits in the human brain, which both promotes tumour progression and impairs cognition