Association of human neuroglobin with cystatin C, a cysteine proteinase inhibitor

Association of human neuroglobin with cystatin C, a cysteine proteinase inhibitor
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DOI:
10.1021/bi0495782
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发表时间:
2004-05-11
期刊:
影响因子:
2.9
通讯作者:
Morishima, I
Morishima, I
中科院分区:
生物学3区
文献类型:
--
作者:
Wakasugi, K;Nakano, T;Morishima, I

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神经珠蛋白(Neuroglobin, Ngb)是一种新发现的在脊椎动物大脑中表达的珠蛋白。据报道,神经元中Ngb水平增加是对缺氧的反应,Ngb保护神经元免受缺氧。然而,这种神经保护的机制尚不清楚。本研究利用酵母双杂交系统鉴定了半胱氨酸蛋白酶抑制剂人胱抑素C为ngb结合蛋白。表面等离子体共振实验证实Ngb与胱抑素C二聚体结合,而不是与单体结合。由于细胞内胱抑素C和淀粉样变胱抑素C形成二聚体,Ngb可能调节胱抑素C的细胞内转运(或分泌),以防止氧化应激条件下的神经元死亡和/或它可能在神经退行性疾病的发生中发挥作用。
Neuroglobin (Ngb) is a newly discovered globin that is expressed in vertebrate brain. It has been reported that Ngb levels increase in neurons in response to oxygen deprivation, and that Ngb protects neurons from hypoxia. However, the mechanism of this neuroprotection remains unclear. In the present study, we identified human cystatin C, a cysteine proteinase inhibitor, as an Ngb-binding protein by using a yeast two-hybrid system. Surface plasmon resonance experiments verified that Ngb binds to cystatin C dimers, not to the monomers. Because both intracellular cystatin C and the amyloidogenic variant of cystatin C form dimers, Ngb may modulate the intracellular transport (or secretion) of cystatin C to protect against neuronal death under conditions of oxidative stress and/or it may have a role in the development 4 neurodegenerative diseases.