Activation of the mitochondrial caspase cascade in the absence of protein synthesis does not require c-Jun N-terminal kinase

Nobuo Watanabe, Takeo Iwamoto, Dale A. Dickinson, Karen E. Iles, Henry Jay Forman

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Prolonged activation of the c-Jun N-terminal kinase (JNK) has been suggested as a signal for apoptosis in response to a wide variety of stimuli. Using three cytocidal RNA or protein synthesis inhibitors (actinomycin D, anisomycin, and emetine), the potential role of JNK in activation of the mitochondrial apoptotic cascade was investigated in A549-S cells. Protein synthesis inhibition per se was not the cause of cell death as cycloheximide induced only growth arrest. All the cytocidal inhibitors induced cytochrome c release and caspases 9 activation within hours, but only anisomycin caused persistent JNK activation. Although, the JNK inhibitor, SP600125, inhibited JNK-dependent anisomycin-induced c-Jun phosphorylation, it was ineffective in preventing anisomycin-induced caspase activation and cell death. Thus, all three lethal macromolecule synthesis inhibitors can activate the mitochondrial apoptotic machinery independent of JNK activation, demonstrating that the mitochondrial apoptotic pathway can be activated independently of the JNK pathway in the absence of protein synthesis.

Original languageEnglish
Pages (from-to)231-240
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume405
Issue number2
DOIs
Publication statusPublished - 2002

Keywords

  • A549
  • Antiapoptotic
  • Caspase
  • Mitochondria
  • Proapoptotic
  • Ribotoxic stress

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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