Senescence marker protein-30 is a unique enzyme that hydrolyzes diisopropyl phosphorofluoridate in the liver

Yoshitaka Kondo, Akihito Ishigami, Sachiho Kubo, Setsuko Handa, Keiko Gomi, Kozo Hirokawa, Naoki Kajiyama, Tsuyoshi Chiba, Kentaro Shimokado, Naoki Maruyama

Research output: Contribution to journalArticle

Abstract

Senescence marker protein-30 (SMP30) was originally identified as a novel protein in the rat liver, the expression of which decreases androgen- independently with aging. We have now characterized a unique property of SMP30, the hydrolysis of diisopropyl phosphorofluoridate (DFP), which is similar to the chemical warfare nerve agents sarine, soman and tabun. Hydrolysis of DFP was stimulated equally well by 1 mM MgCl2, MnCl2 or CoCl 2, to a lesser extent by 1 mM CdCl2 but not at all by 1 mM CaCl2. No 45Ca2+-binding activity was detected for purified SMP30, suggesting that SMP30 is not a calcium-binding protein, as others previously stated. Despite the sequence similarity between SMP30 and a serum paraoxonase (PON), the inability of SMP30 to hydrolyze PON-specific substrates such as paraoxon, dihydrocoumarin, γ-nonalactone, and δ-dodecanolactone indicate that SMP30 is distinct from the PON family. We previously established SMP30 knockout mice and have now tested DFPase activity in their livers. The livers from wild-type mice contained readily detectable DFPase activity, whereas no such enzyme activity was found in livers from SMP30 knockout mice. Moreover, the hepatocytes of SMP30 knockout mice were far more susceptible to DFP-induced cytotoxicity than those from the wild-type. These results indicate that SMP30 is a unique DFP hydrolyzing enzyme in the liver and has an important detoxification effect on DFP. Consequently, a reduction of SMP30 expression might account for the age-associated deterioration of cellular functions and enhanced susceptibility to harmful stimuli in aged tissue.

Original languageEnglish
Pages (from-to)57-62
Number of pages6
JournalFEBS Letters
Volume570
Issue number1-3
DOIs
Publication statusPublished - 2004 Jul 16
Externally publishedYes

Keywords

  • DFP, diisopropyl phosphorofluoridate
  • Diisopropyl phosphorofluoridate
  • LRE, luciferin-regenerating enzyme
  • PLC, phospholipase C
  • PLD, phospholipase D
  • PON, paraoxonase
  • SDS-PAGE, SDS-polyacrylamide gel electrophoresis
  • SMP30, senescence marker protein-30

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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  • Cite this

    Kondo, Y., Ishigami, A., Kubo, S., Handa, S., Gomi, K., Hirokawa, K., Kajiyama, N., Chiba, T., Shimokado, K., & Maruyama, N. (2004). Senescence marker protein-30 is a unique enzyme that hydrolyzes diisopropyl phosphorofluoridate in the liver. FEBS Letters, 570(1-3), 57-62. https://doi.org/10.1016/j.febslet.2004.06.028