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多酚类化合物对组成型蛋白酶体和免疫蛋白酶体蛋白水解活性的影响。

Effect of polyphenolic compounds on the proteolytic activities of constitutive and immuno-proteasomes.

作者信息

Pettinari Assuntina, Amici Manila, Cuccioloni Massimiliano, Angeletti Mauro, Fioretti Evandro, Eleuteri Anna Maria

机构信息

Postgraduate School in Clinical Biochemistry, Department of Molecular, Cellular and Animal Biology, University of Camerino, Camerino, Italy.

出版信息

Antioxid Redox Signal. 2006 Jan-Feb;8(1-2):121-9. doi: 10.1089/ars.2006.8.121.

Abstract

The effect of several polyphenols on the 20S proteasomes, both the constitutive and the LMP proteasomes, isolated from bovine tissues, has been investigated. Polyphenolic compounds show many biological activities such as antiviral, antibacterial, antifungal, anti-inflammatory, antimutagenic, and antiallergic activities. However, the molecular mechanism underlying these effects has not been identified. It is well established that polyphenols possess inhibitory activities on several enzymes and among them the 20S proteasome. In the present work, the ChT-L, BrAAP, PGPH, and T-L activities of the isolated constitutive and immuno-proteasomes were assayed in order to get an overall information on the polyphenols binding to the complexes. The effects of the polyphenols on the proteasomal activities were analyzed, taking into account the different subunits composition of the two complexes. Furthermore the same activities were measured on whole extracts from cancer cells exposed to EGCG and gallic acid, evaluating, also, their antioxidant action under oxidative stress. EGCG and gallic acid are able to affect the 20S proteasomes functionality, depending on the complex subunit composition and, in cell extracts, they behave both as antioxidants and proteasome effectors.

摘要

已对从牛组织中分离出的几种多酚对20S蛋白酶体(包括组成型和LMP蛋白酶体)的作用进行了研究。多酚类化合物具有多种生物活性,如抗病毒、抗菌、抗真菌、抗炎、抗诱变和抗过敏活性。然而,这些作用背后的分子机制尚未明确。众所周知,多酚对多种酶具有抑制活性,其中包括20S蛋白酶体。在本研究中,对分离出的组成型和免疫蛋白酶体的ChT-L、BrAAP、PGPH和T-L活性进行了测定,以便全面了解多酚与这些复合物的结合情况。考虑到两种复合物不同的亚基组成,分析了多酚对蛋白酶体活性的影响。此外,还对暴露于表没食子儿茶素没食子酸酯(EGCG)和没食子酸的癌细胞全提取物进行了相同活性的测定,同时评估了它们在氧化应激下的抗氧化作用。EGCG和没食子酸能够影响20S蛋白酶体的功能,这取决于复合物的亚基组成,并且在细胞提取物中,它们既表现为抗氧化剂,又表现为蛋白酶体效应物。

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