Diisopropylfluorophosphate (DFP) inhibits ricin-induced apoptosis of MDCK cells

Bioscience, Biotechnology, and Biochemistry
T OdaT Muramatsu

Abstract

Diisopropylfluorophosphate (DFP), a general serine protease inhibitor, inhibited the DNA fragmentation and cell death in MDCK cells treated with ricin, modeccin, Pseudomonas toxin, or diphtheria toxin. A trypsin-like serine protease inhibitor, N-tosyl-L-lysine chloromethyl ketone (TLCK) also prevented ricin-induced DNA fragmentation and cell death, albeit less effectively than DFP. Microscopic observation showed that the morphological changes of MDCK cells induced by ricin were prevented by DFP. DFP did not affect the binding, internalization, or subsequent excretion of ricin, but reduced the degradation of ricin in MDCK cells, suggesting that DFP inhibits at least the cellular protease that may be involved in the degradation of internalized ricin. In addition, SDS-PAGE analysis of cytosolic proteins suggested that DFP-sensitive endogenous proteases are activated in the ricin-treated cells. In the cells treated with DFP, the protein synthesis inhibitory activity of ricin was increased rather than inhibited. The activities of modeccin and Pseudomonas toxin were also slightly increased by DFP, but no effect of DFP on the activity of diphtheria toxin was observed. Therefore, these results suggest that protein toxins have a DFP-sen...Continue Reading

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Citations

Jan 11, 2007·Bioscience, Biotechnology, and Biochemistry·Mochammad Amin AlamsjahTatsuya Oda
Jul 9, 2010·Journal of Inflammation·Jennifer Ly TsangJohn C Marshall
May 5, 2001·Annual Review of Plant Physiology and Plant Molecular Biology·Kirsten Nielsen, Rebecca S Boston
Oct 8, 2004·Journal of Biochemistry and Molecular Biology·Xiaoling Qu, Liuting Qing
Apr 8, 1999·Bioscience, Biotechnology, and Biochemistry·T OdaT Muramatsu
May 31, 2002·Bioscience, Biotechnology, and Biochemistry·Ai KageyamaTsuyoshi Muramatsu
Feb 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·J MarshallB Rubin
Jun 5, 2002·Toxicology Letters·Tadashi TamuraTsuyoshi Muramatsu
Feb 5, 2003·Toxicon : Official Journal of the International Society on Toxinology·O KumarR Vijayaraghavan

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis