Inhibition versus induction of apoptosis by proteasome inhibitors depends on concentration

Kuo I. Lin, Jay M. Baraban, Rajiv R. Ratan

Research output: Contribution to journalArticle

Abstract

We previously established that NF-κB DNA binding activity is required for Sindbis Virus (SV)-induced apoptosis. To investigate whether SV induces nuclear translocation of NF-κ-B via the proteasomal degradation pathway, we utilized MG132, a peptide aldehyde inhibitor of the catalytic subunit of the proteasome. 20 μM MG132 completely abrogated SV induced NF-κ-B nuclear activity at early time points after infection. Parallel measures of cell viability 48 h after SV infection revealed that 20 μM MG132 induced apoptosis in uninfected cells. In contrast, a lower concentration of MG132 (200 nM) resulted in partial inhibition of SV-induced nuclear NF-κB activity and inhibition of SV-induced apoptosis without inducing toxicity in uninfected cells. The specific proteasomal inhibitor, lactacystin, also inhibited SV-induced death. Taken together, these results suggest that the pro-apoptotic and antiapoptotic functions of peptide aldehyde proteasome inhibitors such as MG-132 depend on the concentration of inhibitor utilized and expand the list of stimuli requiring proteasomal activation to induce apoptosis to include viruses.

Original languageEnglish (US)
Pages (from-to)577-583
Number of pages7
JournalCell death and differentiation
Volume5
Issue number7
DOIs
StatePublished - Jul 1998

Keywords

  • Apoptosis
  • Proteasome inhibitors
  • Sindbis virus

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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