Specific reaction of alpha,beta-unsaturated carbonyl compounds such as 6-shogaol with sulfhydryl groups in tubulin leading to microtubule damage.
6-Shogaol and 6-gingerol are ginger components with similar chemical structures. However, while 6-shogaol damages microtubules, 6-gingerol does not. We have investigated the molecular mechanism of 6-shogaol-induced microtubule damage and found that the action of 6-shogaol results from the structure of alpha,beta-unsaturated carbonyl compounds. alpha,beta-Unsaturated carbonyl compounds such as 6-shogaol react with sulfhydryl groups of cysteine residues in tubulin, and impair tubulin polymerization. The reaction with sulfhydryl groups depends on the chain length of alpha,beta-unsaturated carbonyl compounds. In addition, alpha,beta-unsaturated carbonyl compounds are more reactive with sulfhydryl groups in tubulin than in 2-mercaptoethanol, dithiothreitol, glutathione and papain, a cysteine protease.
Ishiguro
Kazuhiro
K
Molecular Biology and Pathogenesis of Gastroenterology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. kio@med.nagoya-u.ac.jp
Ando
Takafumi
T
Watanabe
Osamu
O
Goto
Hidemi
H
D002396:Catechols / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D005233:Fatty Alcohols / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D014404:Tubulin / Q000378:metabolism*
D002396:Catechols; D005233:Fatty Alcohols; D014404:Tubulin; C040115:shogaol; C007845:gingerol; D003545:Cysteine