Mechanism of destruction of microtubule structures by 4-hydroxy-2-nonenal

June Kokubo, Naoki Nagatani, Katsunori Hiroki, Kenji Kuroiwa, Nobuo Watanabe, Takao Arai

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)51-59
Number of pages9
JournalCell structure and function
Issue number1
Publication statusPublished - 2008


  • Cytoskeleton
  • Electrophile
  • Protein modification
  • Redox regulation
  • Tubulin

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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