Mechanism of Destruction of Microtubule Structures by 4-Hydroxy-2-Nonenal

Cell Structure and Function

Naoki Nagatani¹  Takao Arai¹  June Kokubo¹  Katsunori Hiroki¹  Kenji Kuroiwa¹  Nobuo Watanabe¹ 

[1] Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science

关键词: tubulin;    electrophile;    protein modification;    cytoskeleton;    redox regulation;   

DOI  :  10.1247/csf.07038

学科分类：分子生物学，细胞生物学和基因

来源: Japan Society for Cell Biology

【 摘 要 】

References(31)Cited-By(10)A major end product of lipid peroxidation, 4-hydroxy-2-nonenal (HNE), is an electrophilic alkenal and produces Michael adducts with cellular proteins. It is known that exposure of cultured cells to HNE causes rapid disappearance of microtubule networks. In this study we addressed the mechanism. Immunochemical studies revealed that HNE preferentially modified α-tubulin in rat primary neuronal cells, PC12 cells, and rat fibroblast cell line 3Y1 cells. This was morphologically associated with the disappearance of microtubule structures in those cells. In a purified rat brain microtubule fraction, HNE modified unpolymerized tubulin and impaired its polymerizability, with a concomitant increase in insolubilized tubulin. Nevertheless, HNE had a marginal effect on the stability of pre-polymerized microtubules. These results suggest that disruption of microtubule assembly as a result of HNE modification of unpolymerized tubulin, rather than destruction of assembled microtubules, is responsible for the disappearance of microtubule structures in cells exposed to HNE.

【 授权许可】

Unknown