Decreased intracellular superoxide levels activate Sindbis virus- induced apoptosis

Kuo I. Lin, Piera Pasinelli, Robert H. Brown, J Marie Hardwick, Rajiv R. Ratan

Research output: Contribution to journalArticle

Abstract

Infection of many cultured cell types with Sindbis virus (SV), an alphavirus, triggers apoptosis through a commonly utilized caspase activation pathway. However, the upstream signals by which SV activates downstream apoptotic effectors, including caspases, remain unclear. Here we report that in AT-3 prostate carcinoma cells, SV infection decreases superoxide (O2- ) levels within minutes of infection as monitored by an aconitase activity assay. This SV-induced decrease in O2- levels appears to activate or modulate cell death, as a recombinant SV expressing the O2- scavenging enzyme, copper/zinc superoxide dismutase (SOD), potentiates SV-induced apoptosis. A recombinant SV expressing a mutant form of SOD, which has reduced SOD activity, has no effect. The potentiation of SV-induced apoptosis by wild type SOD is because of its ability to scavenge intracellular O2- rather than its ability to promote the generation of hydrogen peroxide. Pyruvate, a peroxide scavenger, does not affect the ability of wild type SOD to potentiate cell death; and increasing the intracellular catalase activity via a recombinant SV vector has no effect on SV-induced apoptosis. Moreover, increasing intracellular O2- by treatment of 3T3 cells with paraquat protects them from SV-induced death. Altogether, our results suggest that SV may activate apoptosis by reducing intracellular superoxide levels and define a novel redox signaling pathway by which viruses can trigger cell death.

Original languageEnglish (US)
Pages (from-to)13650-13655
Number of pages6
JournalJournal of Biological Chemistry
Volume274
Issue number19
DOIs
StatePublished - May 7 1999

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ASJC Scopus subject areas

  • Biochemistry

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