Journal of Antivirals & Antiretrovirals
Open Access

H₂O₂ signals via iron induction of VL30 retrotransposition correlated with cytotoxicity

2^nd 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