title: Mechanism of destruction of microtubule structures by 4-hydroxy-2-nonenal.
abstract: 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 alpha-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.
authors: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Chiba, Japan.
authors: June
authors: J
authors: Kokubo
authors: Naoki
authors: N
authors: Nagatani
authors: Katsunori
authors: K
authors: Hiroki
authors: Kenji
authors: K
authors: Kuroiwa
authors: Nobuo
authors: N
authors: Watanabe
authors: Takao
authors: T
authors: Arai
mesh_terms: D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000166:cytology; D002460:Cell Line; D007120:Immunochemistry; D008870:Microtubules / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011108:Polymers / Q000737:chemistry; D051381:Rats; D013379:Substrate Specificity; D014404:Tubulin / Q000378:metabolism
chemical_list: D000447:Aldehydes; D011108:Polymers; D014404:Tubulin; C027576:4-hydroxy-2-nonenal