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      • KCI등재

        Functional and Structural Effects of Amyloid-beta Aggregate on Xenopus laevis Oocytes

        Jorge Parodi,Ataúlfo Martínez-Torres,Lenin Ochoa-de la Paz,Ricardo Miledi 한국분자세포생물학회 2012 Molecules and cells Vol.34 No.4

        Xenopus laevis oocytes exposed to amyloid- aggregate generated oscillatory electric activity (blips) that was recorded by two-microelectrode voltage-clamp. The cells exhibited a series of “spontaneous” blips ranging in amplitude from 3.8  0.9 nA at the beginning of the recordings to 6.8  1.7 nA after 15 min of exposure to 1 M aggregate. These blips were similar in amplitude to those induced by the channel-forming antimicrobial agents amphotericin B (7.8  1.2 nA) and gramicidin (6.3  1.1 nA). The amyloid aggregate-induced currents were abolished when extracellular Ca2+ was removed from the bathing solution, suggesting a central role for this cation in generating the spontaneous electric activity. The amyloid aggregate also affected the Ca2+-dependent Cl- currents of oocytes, as shown by increased amplitude of the transient-outward chloride current (Tout) and the serum-activated, oscillatory Cl- currents. Electron microcopy revealed that amyloid aggregate induced the dissociation of the follicular cells that surround the oocyte, thus leading to a failure in the electro-chemical communication between these cells. This was also evidenced by the suppression of the oscillatory Ca2+-dependent ATP-currents, which require proper coupling between oocytes and the follicular cell layer. These observations, made using the X. laevis oocytes as a versatile experimental model, may help to understand the effects of amyloid aggregate on cellular communication.

      • SCIESCOPUSKCI등재

        Contributed Mini Review : Amyloid pore-channel hypothesis: effect of ethanol on aggregation state using frog oocytes for an Alzheimer`s disease study

        ( Jorge Parodi ),( David Ormeno ),( Lenin D. Ochoa De La Paz ) 생화학분자생물학회 2015 BMB Reports Vol.48 No.1

        Alzheimer``s disease severely compromises cognitive function. One of the mechanisms to explain the pathology of Alzheimer’sdisease has been the hypotheses of amyloid-pore/channel formationby complex Aβ-aggregates. Clinical studies suggestedthe moderate alcohol consumption can reduces probability developingneurodegenerative pathologies. A recent report exploredthe ability of ethanol to disrupt the generation of complexAβ in vitro and reduce the toxicity in two cell lines. Molecular dynamics simulations were applied to understandhow ethanol blocks the aggregation of amyloid. On the otherhand, the in silico modeling showed ethanol effect over thedynamics assembling for complex Aβ-aggregates mediated bybreak the hydrosaline bridges between Asp 23 and Lys 28, wasare key element for amyloid dimerization. The amyloid pore/channel hypothesis has been explored only in neuronal models,however recently experiments suggested the frog oocytessuch an excellent model to explore the mechanism of the amyloidpore/channel hypothesis. So, the used of frog oocytes toexplored the mechanism of amyloid aggregates is new, mainlyfor amyloid/pore hypothesis. Therefore, this experimentalmodel is a powerful tool to explore the mechanism implicatesin the Alzheimer’s disease pathology and also suggests a modelto prevent the Alzheimer’s disease pathology.

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