کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10958344 | 1100014 | 2010 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
H2O2 and PAF mediate Aβ1-42-induced Ca2+ dyshomeostasis that is blocked by EGb761
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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چکیده انگلیسی
Calcium (Ca2+) dyshomeostasis may be of pivotal importance in mediating the neurotoxic action of amyloid β peptide (Aβ), but the mechanism whereby Aβ disrupts Ca2+ homeostasis remains unclear. Using hippocampal neuronal cultures, the present study investigated possible mechanisms underlying Ca2+ dyshomeostasis induced by the oligomeric form of Aβ1-42 and two possible mediators of its toxicity, hydrogen peroxide (H2O2) and platelet-activating factor (PAF). It was found that, both H2O2 and PAF were able to reproduce each of the events induced by oligomeric Aβ1-42, including (a) Ca2+ influx via N-methyl-d-aspartic acid (NMDA) receptors, (b) enhancement of Ca2+ response to NMDA via activation of protein kinase C (PKC), (c) the increase of extracellular concentrations of glutamate and (d) the increase in cytosolic free Ca2+ ([Ca2+]i). Moreover, each of these events could be blocked by Ginkgo biloba extract EGb761, a free radical scavenger with PAF antagonism, and by quercetin, a constituent with well-established free radical scavenging property. In contrast, ginkgolide B, another constituent of EGb761 with well-established PAF-antagonizing activity protected the neurons against Ca2+ dyshomeostasis induced by Aβ1-42 and PAF, but not by H2O2. These results suggested the possibility that Aβ1-42-induced Ca2+ dyshomeostasis might be mediated by formation of toxic mediators such as H2O2 and PAF. Therefore, increased production of toxic mediators such as H2O2 and PAF in the brain may be critical in the pathological mechanism of neurodegenerative diseases, particularly Alzheimer's disease (AD), and may serve as major therapeutic targets for these diseases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 56, Issue 8, July 2010, Pages 893-905
Journal: Neurochemistry International - Volume 56, Issue 8, July 2010, Pages 893-905
نویسندگان
Chun Shi, Fengming Wu, Jie Xu,