Isolated ricin b-chain-mediated apoptosis in u937 cells

Naoko Hasegawa, Yoshinobu Kimura, Tatsuya Oda, Nobukazu Komatsu, Tsuyoshi Muramatsu

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

We have previously reported that ricin, a toxic lectin that inhibits protein synthesis induced apoptotic cell death. In this study, we have found that isolated ricin CM-B-chain, which has no effect on cellular protein synthesis, induced DNA fragmentation in U937 cells in a dose- and time-dependent manner, albeit it required a longer incubation time and higher concentration than those of holotoxin ricin. Z-Asp-CH2-DCB, a caspase family inhibitor and serine protease inhibitor, 3,4-dichloroisocoumarine (DCI) effectively inhibited the CM-B-chain-mediated DNA fragmentation as well as in ricin. Thus, like ricin, multiple proteases with different substrate specificity may also be involved in the CM-B-chain-mediated apoptotic pathway. Furthermore, BFA inhibited both ricin- and CM-B-chain-mediated DNA fragmentation, suggesting an intracellular vesicle transport system through the Golgi complex may be involved in the apoptotic induction by these proteins as a common feature. On the other hand, cycloheximide (CHA) strongly increased the CM-B-chain-mediated DNA fragmentation, but inhibited ricin-mediated DNA fragmentation. The opposite effects of CHA may reflect the difference in the apoptotic mechanism between ricin and CM-B-chain. In conclusion, our results suggest that ricin-B-chain can induce apoptosis through its lectin activity, but the underlying mechanism may be distinct from that of ricin in which the A-chain contributes profoundly to the apoptotic induction.

Original languageEnglish
Pages (from-to)1422-1429
Number of pages8
JournalBioscience, Biotechnology and Biochemistry
Volume64
Issue number7
DOIs
Publication statusPublished - Jan 1 2000

Keywords

  • Apoptosis
  • Cytotoxicity
  • Lectin
  • Ricin
  • Ricin B-chain

ASJC Scopus subject areas

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

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