Amyloid-β inhibits No-cGMP signaling in a CD36- and CD47-dependent manner.
Amyloid-β inhibits No-cGMP signaling in a CD36- and CD47-dependent manner.
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DOI：
10.1371/journal.pone.0015686
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发表时间：
2010-12-22
期刊：
影响因子：
3.7
通讯作者：
Roberts DD
中科院分区：
文献类型：
--
作者：
Miller TW;Isenberg JS;Shih HB;Wang Y;Roberts DD
淀粉样蛋白-β 与两种细胞表面受体 CD36 和 CD47 相互作用，基质细胞蛋白血小板反应蛋白-1 通过这两种受体抑制可溶性鸟苷酸环化酶的激活。在这里，我们检查淀粉样蛋白-β是否具有这种抑制活性。淀粉样蛋白-β 可抑制多种细胞类型中药物和一氧化氮介导的可溶性鸟苷酸环化酶的激活。已知血小板和血管平滑肌细胞中对一氧化氮的 cGMP 依赖性功能反应相应地受到淀粉样蛋白-β 的抑制。淀粉样蛋白-β 与清道夫受体 CD36 的功能性相互作用通过该受体抑制游离脂肪酸的摄取来表明。可溶性低聚物和纤维状β淀粉样蛋白均具有活性。相反，淀粉样蛋白-β 不会与已知的配体 SIRPα 竞争与 CD47 的结合。然而，这两种受体都是β淀粉样蛋白抑制cGMP积累所必需的。这些数据表明，淀粉样蛋白-β 与 CD36 的相互作用会诱导 CD47 依赖性信号，抑制可溶性鸟苷酸环化酶的激活。结合通过 CD36 抑制游离脂肪酸转运的多效性作用，这些数据提供了一种分子机制，β-淀粉样蛋白可以通过该分子机制导致与阿尔茨海默病相关的一氧化氮信号传导缺陷。
Amyloid-β interacts with two cell surface receptors, CD36 and CD47, through which the matricellular protein thrombospondin-1 inhibits soluble guanylate cyclase activation. Here we examine whether amyloid-β shares this inhibitory activity. Amyloid-β inhibited both drug and nitric oxide-mediated activation of soluble guanylate cyclase in several cell types. Known cGMP-dependent functional responses to nitric oxide in platelets and vascular smooth muscle cells were correspondingly inhibited by amyloid-β. Functional interaction of amyloid-β with the scavenger receptor CD36 was indicated by inhibition of free fatty acid uptake via this receptor. Both soluble oligomer and fibrillar forms of amyloid-β were active. In contrast, amyloid-β did not compete with the known ligand SIRPα for binding to CD47. However, both receptors were necessary for amyloid-β to inhibit cGMP accumulation. These data suggest that amyloid-β interaction with CD36 induces a CD47-dependent signal that inhibits soluble guanylate cyclase activation. Combined with the pleiotropic effects of inhibiting free fatty acid transport via CD36, these data provides a molecular mechanism through which amyloid-β can contribute to the nitric oxide signaling deficiencies associated with Alzheimer's disease.
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DOI：
10.1111/j.1749-6632.1997.tb48507.x
发表时间：
1997-09-26
影响因子：
5.2
作者：
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