A loss in cellular protein partners promotes α-synuclein aggregation in cells resulting from oxidative stress.
A loss in cellular protein partners promotes α-synuclein aggregation in cells resulting from oxidative stress.
复制标题
细胞蛋白伴侣的丧失会促进氧化应激引起的细胞中α-突触核蛋白聚集。
DOI：
10.1021/bi4002425
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发表时间：
2013-06-04
期刊：
影响因子：
2.9
通讯作者：
Scarlata S
中科院分区：
文献类型：
--
作者：
Guo Y;Scarlata S
有一个共识，氧化应激促进神经退行性变，并可能与斑块形成有关。α-突触核蛋白是神经退行性斑块的主要成分。我们发现α-突触核蛋白在体外和细胞中与磷脂酶Cβ1 （PLCβ1）紧密结合，影响其G蛋白的活化和降解。由于PLCβ1在细胞中与α-synuclein结合，我们测试了降低其水平是否会促进α-synuclein的聚集，以及过量产生PLCβ1是否会抑制α-synuclein的聚集。通过对HEK293、PC12和SK-H-SH细胞中α-synuclein的荧光成像，我们发现α-synuclein的聚集与plc - β1的水平有直接关系。重要的是，我们发现氧化应激不影响α-synuclein的细胞水平，但导致PLCβ1的下调，从而促进α-synuclein的聚集。一种模仿部分α-突触核蛋白与PLCβ结合位点的肽可以防止聚集。我们的研究表明，PLCβ1可以减少氧化应激下的细胞损伤，并提供了一个可能被利用来阻止α-突触核蛋白聚集的潜在位点。
There is a consensus that oxidative stress promotes neurodegeneration and may be linked to plaque formation. α-Synuclein is the main component of neurodegenerative plaques. We have found that α-synuclein binds strongly to the enzyme phospholipase Cβ1 (PLCβ1) in vitro and in cells affecting both its G protein activation and its degradation. Because PLCβ1 binds to α-synuclein in cells, we tested whether decreasing its level would promote α-synuclein aggregation and whether overproducing PLCβ1 would inhibit aggregation. By imaging fluorescent α-synuclein in living HEK293, PC12, and SK-H-SH cells, we find that α-synuclein aggregation is directly related to the level of PLCβ1. Importantly, we found that oxidative stress does not affect the cellular levels of α-synuclein but results in the down-regulation of PLCβ1 thereby promoting α-synuclein aggregation. A peptide that mimics part of the α-synuclein binding site to PLCβ prevents aggregation. Our studies indicate that PLCβ1 can reduce cell damage under oxidative stress and offers a potential site that might be exploited to prevent α-synuclein aggregation.