Inhibition of virus-induced neuronal apoptosis by Bax

Jennifer Lewis, George A. Oyler, Kazuyoshi Ueno, Yih Ru Fannjiang, B. Nelson Chau, James Vornov, Stanley J. Korsmeyer, Shifa Zou, J. Marie Hardwick

Research output: Contribution to journalArticle

Abstract

The Bax protein is widely known as a pro-apoptotic Bcl-2 family member that when overexpressed can trigger apoptosis in multiple cell types and is important for the developmental cell death of neurons. However, Bax was found here to be a potent inhibitor of neuronal cell death in mice infected with Sindbis virus. Newborn mice, which are highly susceptible to a fatal infection with neurotropic Sindbis virus, were significantly protected from neuronal apoptosis and fatal disease when infected with a recombinant Sindbis virus encoding Bax. Deletion of the N terminus of Bax, which mimics cleaved Bax, converted Bax into a pro-apoptotic factor in vivo. As mice mature during the first week after birth, they acquire resistance to a fatal Sindbis virus infection. However, Bax-deficient mice remained very sensitive to fatal disease compared with their control littermates, indicating that endogenous Bax functions as a survival factor and contributes to age-dependent resistance to Sindbis virus-induced mortality. The protective effects of Bax were reproduced in cultured hippocampal neurons but not in cultured dorsal root ganglia neurons. These findings indicate that cell-specific factors determine the anti-apoptotic versus pro-apoptotic function of Bax.

Original languageEnglish (US)
Pages (from-to)832-835
Number of pages4
JournalNature medicine
Volume5
Issue number7
DOIs
StatePublished - Jul 1999

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Lewis, J., Oyler, G. A., Ueno, K., Fannjiang, Y. R., Chau, B. N., Vornov, J., Korsmeyer, S. J., Zou, S., & Hardwick, J. M. (1999). Inhibition of virus-induced neuronal apoptosis by Bax. Nature medicine, 5(7), 832-835. https://doi.org/10.1038/10556