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

Fingerprint

Sindbis Virus
Viruses
Superoxides
Apoptosis
Superoxide Dismutase
Cell death
Cell Death
Caspases
Effector Caspases
Aconitate Hydratase
Alphavirus
Cells
3T3 Cells
Paraquat
Peroxides
Virus Diseases
Scavenging
Infection
Pyruvic Acid
Catalase

ASJC Scopus subject areas

  • Biochemistry

Cite this

Decreased intracellular superoxide levels activate Sindbis virus- induced apoptosis. / Lin, Kuo I.; Pasinelli, Piera; Brown, Robert H.; Hardwick, J Marie; Ratan, Rajiv R.

In: Journal of Biological Chemistry, Vol. 274, No. 19, 07.05.1999, p. 13650-13655.

Research output: Contribution to journalArticle

Lin, Kuo I. ; Pasinelli, Piera ; Brown, Robert H. ; Hardwick, J Marie ; Ratan, Rajiv R. / Decreased intracellular superoxide levels activate Sindbis virus- induced apoptosis. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 19. pp. 13650-13655.
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