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Evaluation of Caspase Activation to Assess Innate Immune Cell Death
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T-2 toxin initially activates caspase-2 and induces apoptosis in U937 cells

Peixin Huang1, Keisuke Akagawa, Yoshiko Yokoyama

  • 1Department of Social and Environmental Medicine, Osaka University Graduate School of Medicine, Yamada-Oka 2-2, Suita, Osaka 565-0871, Japan.

Toxicology Letters
|March 30, 2007
PubMed

Insights

T-2 toxin, a mycotoxin from Fusarium fungi, triggers apoptosis in U937 cells by activating caspase-2. This early caspase-2 activation is crucial for subsequent caspase-8 and caspase-3 signaling, driving programmed cell death.

Area of Science:

  • Toxicology
  • Cell Biology
  • Biochemistry

Background:

  • Mycotoxins, such as T-2 toxin produced by Fusarium fungi, are common natural contaminants.
  • T-2 toxin exposure can lead to significant cellular damage and apoptosis.

Purpose of the Study:

  • To investigate the specific mechanisms of T-2 toxin-induced apoptosis in U937 cells.
  • To identify the key caspases involved in the apoptotic pathway initiated by T-2 toxin.

Main Methods:

  • U937 cells were treated with varying concentrations of T-2 toxin.
  • Assays were performed to assess cell viability, DNA fragmentation, ATP levels, and mitochondrial respiratory chain complex activity.
  • Western blot analysis and enzyme activity assays were used to detect caspase activation (caspase-2, -3, -8, -9).
  • Specific caspase inhibitors were employed to elucidate the signaling pathway.

Main Results:

  • T-2 toxin concentrations above 10nM induced significant apoptosis, characterized by nuclear fragmentation and caspase-3 activation.
  • Caspase-2, -3, -8, and -9 were all activated by T-2 toxin.
  • T-2 toxin did not inhibit mitochondrial respiration or decrease ATP levels.
  • Enzyme activity assays and Western blots showed earlier activation of caspase-2 compared to other caspases.
  • Inhibitors of caspase-2 and caspase-8 effectively blocked procaspase-3 activation, while caspase-9 inhibition was less effective.
  • Caspase-2 inhibition completely prevented the activation of caspase-8 and -9.

Conclusions:

  • Caspase-2 activation is essential for T-2 toxin-induced apoptosis in U937 cells.
  • The primary apoptotic signaling pathway involves caspase-2, leading to the activation of caspase-8 and caspase-3, rather than the mitochondrial pathway.

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