Journal of Antivirals & Antiretrovirals

Journal of Antivirals & Antiretrovirals
Open Access

ISSN: 1948-5964

+44 1300 500008

H2O2 signals via iron induction of VL30 retrotransposition correlated with cytotoxicity


2nd International Conference on Retroviruses and Novel Drugs

June 30-July 01, 2016 Cape Town, South Africa

Dimitrios Noutsopoulos

Laboratory of General Biology, Medical School, University of Ioannina, Greece.

Posters & Accepted Abstracts: J Antivir Antiretrovir

Abstract :

The impact of oxidative stress on mobilization of endogenous retroviruses and their effects on cell fate is unknown. We investigated the action of H2O2 on retrotransposition of an EGFP-tagged mouse LTR-retrotransposon, VL30, in an NIH3T3 cell-retrotransposition assay. H2O2 treatment of assay cells caused specific retrotranspositions documented by UV microscopy and PCR analysis. Flow cytometric analysis revealed an unusually high dose- and time-dependent retrotransposition frequency induced, ~420,000-fold at 40 mM H2O2 compared to the natural frequency, which was reduced by ectopic expression of catalase. Remarkably, H2O2 moderately induced the RNA expression of retrotransposon B2 without affecting the basal expression of VL30s and L1 and significantly induced the expression of various endogenous reverse transcriptase genes. Further, whereas treatment with 50 mM FeCl2 alone was ineffective, cotreatment with 10 mM H2O2 and 50 mM FeCl2 caused a 6-fold higher retrotransposition induction than H2O2 alone, which was associated with cytotoxicity. H2O2 - or H2O2 /FeCl2-induced retrotransposition was significantly reduced by the iron chelator DFO or the antioxidant NAC, respectively. Furthermore, both H2O2 -induced retrotransposition and associated cytotoxicity were inhibited after pretreatment of cells with DFO or the reverse transcriptase inhibitors efavirenz and etravirine. Our data show for the first time that H2O2 , acting via iron, is a potent stimulus of retrotransposition contributing to oxidative stress-induced cell damage.

Biography :

Email: dnoutso@cc.uoi.gr

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