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 language | English (US) |
---|---|
Pages (from-to) | 577-583 |
Number of pages | 7 |
Journal | Cell death and differentiation |
Volume | 5 |
Issue number | 7 |
DOIs | |
State | Published - Jul 1998 |
Keywords
- Apoptosis
- Proteasome inhibitors
- Sindbis virus
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology