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[(14)C]丙烯酰胺在小鼠神经系统中与蛋白质的体内结合。

In vivo binding of [(14)C]acrylamide to proteins in the mouse nervous system.

作者信息

Carrington C D, Lapadula D M, Dulak L, Friedman M, Abou-Donia M B

机构信息

Department of Pharmacology, Duke University Medical Center, Box 3813, Durham, NC 27710, U.S.A.

出版信息

Neurochem Int. 1991;18(2):191-7. doi: 10.1016/0197-0186(91)90185-g.

Abstract

The labeling of mouse brain and spinal cord proteins in vivo following the administration of 200 ?g/kg [(14)C]acrylamide (25 mCi/kg, i.p.) was measured by polyacrylamide gel electrophoresis and autoradiography. Several cytoskeletal proteins had the highest specific activity. These included the medium (130 kDa) and high (180 kDa) molecular weight neurofilament proteins and unknown proteins with molecular weights of 31, 33 and 57 kDa. About 0.05% of the neurofilament proteins were labeled with the dose employed. Although accurate assessments of the stoichiometry for acrylamide binding to 31, 33 and 57 kDa bands could not be made due to the low concentrations of these proteins, it is estimated that over 0.1% of these proteins bound acrylamide. There were significant amounts of acrylamide bound to proteins seven days after exposure, with labeling ranging from 15 to 60% of the levels observed one day after exposure. These results show that acrylamide binds to several major cytoskeletal proteins present in the mouse nervous system. The formation of these adducts may play a role in the neurotoxicity of acrylamide.

摘要

通过聚丙烯酰胺凝胶电泳和放射自显影法测量给予200 μg/kg [¹⁴C]丙烯酰胺(25 mCi/kg,腹腔注射)后小鼠脑和脊髓蛋白质在体内的标记情况。几种细胞骨架蛋白具有最高的比活性。这些蛋白包括中等分子量(130 kDa)和高分子量(180 kDa)的神经丝蛋白以及分子量为31、33和57 kDa的未知蛋白。所使用的剂量标记了约0.05%的神经丝蛋白。尽管由于这些蛋白浓度较低,无法准确评估丙烯酰胺与31、33和57 kDa条带结合的化学计量,但估计超过0.1%的这些蛋白结合了丙烯酰胺。暴露七天后,有大量丙烯酰胺与蛋白质结合,标记水平为暴露一天后观察到的水平的15%至60%。这些结果表明丙烯酰胺与小鼠神经系统中存在的几种主要细胞骨架蛋白结合。这些加合物的形成可能在丙烯酰胺的神经毒性中起作用。

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