The goal of this project is to establish the physiological and pathophysiological functions of endogenous electrophiles originated from membrane lipids in life style-related diseases as well as their utility as the molecular probes for clinical diagnosis. In addition to the basic and applied biological sciences on endogenous electrophiles, we also conduct chemical and biological studies on food-originated bioactive components that modulate the ability of cells and organisms to withstand the electrophile-induced stress.

• Uchida, K., Kanematsu, M., Sakai, K., Matsuda, M., Hattori, N., Mizuno, Y., Suzuki, D., Miyata, T., Noguchi, N., Niki, E., and Osawa, T. (1998) Protein-bound acrolein: potential markers for oxidative stress. Proc. Natl. Acad. Sci. U.S.A. 95, 4882-4887.

• Uchida, K., Kanematsu, M., Morimitsu, Y., Osawa, T., Noguchi, N., and Niki, E. (1998) Acrolein is a product of lipid peroxidation reaction. Formation of acrolein and its conjugate with lysine residues in oxidized low-density lipoprotein. J. Biol. Chem. 273, 16058-16066.
  
  

• Kawamoto, Y., Nakamura, Y., Naito, Y., Torii, Y., Kumagai, T., Osawa, T., Ohigashi, H., Satoh, K., Imagawa, M., and Uchida, K. (2000) Cyclopentenone prostaglandins as potential inducers of phase II detoxification enzyme: 15-deoxy-Δ^12,14-prostaglandin J₂-induced expression of glutathione S-transferases. J. Biol. Chem. 275, 11291-11299.
  
  
• Kondo, M., Oya-Ito, T., Kumagai, T., Osawa, T., and Uchida, K. (2001) Cyclopentenone prostaglandins as potential inducers of intracellular oxidative stress. J. Biol. Chem. 276, 12076-12083.
  
  
• Morimitsu, Y., Nakagawa, Y., Hayashi, H., Fujii, H., Kumagai, T., Nakamura, Y., Osawa, T., Horio, F., Itoh, K., Iida, K., Yamamoto, M., and Uchida, K. (2002) A sulforaphane analogue that potently activates the Nrf2-dependent detoxification pathway. J. Biol. Chem. 277, 3456-3463.
  
  
• Shibata, T., Kondo, M., Osawa, T., Shibata, N., Kobayashi, M., and Uchida, K. (2002) 15-Deoxy-Δ^12,14-prostaglandin J₂: A prostaglandin D₂ metabolite generated during inflammatory processes. J. Biol. Chem. 277, 10459-10466.
  
  
• Kondo, M., Shibata, T., Kumagai, T., Osawa, T., Shibata, N., Kobayashi, M., Sasaki, S., Iwata, M., Noguchi, N., and Uchida, K. (2002) 15-Deoxy-Δ^12,14-prostaglandins J₂: The endogenous electrophile that induces neuronal apoptosis. Proc. Natl. Acad. Sci. U.S.A. 99, 7367-7372.
  
  
• Furuhata, A., Nakamura, M., Osawa, T., and Uchida, K. (2002) Thiolation of protein-bound carcinogenic aldehyde: An electrophilic acrolein-lysine adduct that covalently binds to thiols. J. Biol. Chem. 277, 27919-27926.
  
  
• Hashimoto, M., Shibata, T., Wasada, H., Toyokuni, S., and Uchida, K. (2003) Structural basis of protein-bound endogenous aldehydes: Chemical and immunochemical characterizations of configurational isomers of a 4-hydroxy-2-nonenal-histidine adduct. J. Biol. Chem. 278, 5044-5051.
  
  
• Shibata, T., Yamada, T., Ishii, T., Kumazawa, S., Nakamura, H., Masutani, H., Yodoi, J., and Uchida, K. (2003) Thioredoxin as a molecular target of cyclopentenone prostaglandins. J. Biol. Chem. 278, 26046-26054.