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蓝莓对C-2神经酰胺破坏毒蕈碱型乙酰胆碱受体转染的COS-7细胞中Ca2+反应及恢复的拮抗作用。

Blueberry antagonism of C-2 ceramide disruption of Ca2+ responses and recovery in MAChR-transfected COS-7 cell.

作者信息

Joseph James A, Neuman Anna, Bielinski Donna F, Fisher Derek R

机构信息

USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St., Boston, MA 02111, USA.

出版信息

J Alzheimers Dis. 2008 Nov;15(3):429-41. doi: 10.3233/jad-2008-15309.

Abstract

Research indicates that muscarinic receptors (MAChRs) may show selective declines in sensitivity during aging and Alzheimer's disease (AD), and these decrements may be related to oxidative stress sensitivity. M1AChR - transfected COS-7 cells exhibit greater decrements in Ca;{2+} buffering following oxotremorine-induced depolarization than M3 cells. This loss, induced via dopamine (DA) or amyloid-beta (Abeta), is similar to those reported in many studies with respect to aging and AD, but were antagonized by blueberry (BB) treatment. However, they may be exacerbated by ceramide which shows considerable increases in AD and aging. Thus, the effects of DA, Abeta_{42} and/or BB were assessed on calcium parameters (e.g., calcium buffering) in the presence or absence of ceramide in M1 and M3 transfected cells. Results indicated that while ceramide did not produce profound deficits in calcium buffering, in either M1- or M3-transfected COS-7 cells, decrements were seen in the ability of M1- and M3-transfected cells to initially respond to oxotremorine, regardless of DA or Abeta_{42} exposure. BB pre-treatment (prior to ceramide) antagonized the ceramide treatment in M1-transfected cells but not M3-transfected cells, where ceramide suppressed BB effects. Results are discussed in terms of the effects on lipid induced changes in plasma membranes.

摘要

研究表明,毒蕈碱受体(MAChRs)在衰老和阿尔茨海默病(AD)过程中可能会出现敏感性的选择性下降,并且这些下降可能与氧化应激敏感性有关。与M3细胞相比,转染了M1AChR的COS-7细胞在氧化震颤素诱导的去极化后,Ca²⁺缓冲能力的下降幅度更大。这种由多巴胺(DA)或β-淀粉样蛋白(Aβ)诱导的损失,与许多关于衰老和AD的研究报告相似,但蓝莓(BB)处理可拮抗这种损失。然而,神经酰胺可能会加剧这种损失,神经酰胺在AD和衰老过程中显著增加。因此,在转染了M1和M3的细胞中,评估了在存在或不存在神经酰胺的情况下,DA、Aβ₄₂和/或BB对钙参数(如钙缓冲)的影响。结果表明,虽然神经酰胺在转染了M1或M3的COS-7细胞中均未导致钙缓冲能力出现严重缺陷,但无论是否暴露于DA或Aβ₄₂,转染了M1和M3的细胞对氧化震颤素的初始反应能力均出现下降。BB预处理(在神经酰胺之前)可拮抗转染了M1的细胞中的神经酰胺处理,但不能拮抗转染了M3的细胞中的神经酰胺处理,在转染了M3的细胞中神经酰胺会抑制BB的作用。本文从脂质对质膜诱导变化的影响方面对结果进行了讨论。

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