Journal article
Decreasing peroxiredoxin II expression decreases glutathione, alters cell cycle distribution, and sensitizes glioma cells to ionizing radiation and H2O2
Free radical biology & medicine, Vol.45(8), pp.1178-1189
07/27/2008
DOI: 10.1016/j.freeradbiomed.2008.07.015
PMCID: PMC2628750
PMID: 18718523
Abstract
Glioblastomas are notorious for their resistance to ionizing radiation (IR) and chemotherapy. We hypothesize that this resistance to IR is due, in part, to alterations in antioxidant enzymes. Here, we show that rat and human glioma cells overexpress the antioxidant enzyme, peroxiredoxin II (Prx II). Glioma cells in which Prx II is decreased using shRNA exhibit increased hyper-oxidization of the remaining cellular Prxs suggesting that the redox environment is more oxidizing. Of interest, decreasing Prx II does not alter other antioxidant enzymes (i.e. catalase, GPx, Prx I, Prx III, CuZnSOD, and MnSOD). Analysis of the redox environment revealed that decreasing Prx II increased intracellular ROS in 36B10 cells; extracellular levels of H
2
O
2
were also increased in both C6 and 36B10 cells. Treatment with H
2
O
2
led to a further elevation in intracellular ROS in cells where Prx II was decreased. Decreasing Prx II expression in glioma cells also reduced clonogenic cell survival following exposure to IR and H
2
O
2
. Furthermore, lowering Prx II expression decreased intracellular glutathione and resulted in a significant decline in glutathione reductase activity, suggesting a possible mechanism for the observed increased sensitivity to oxidative insults. Additionally, decreasing Prx II expression increased cell cycle doubling times with less cells distributed to S-phase in C6 glioma cells and more cells redistributed to the most radiosensitive phase of cell cycle, G2/M, in 36B10 glioma cells. These findings support the hypothesis that inhibiting Prx II sensitizes glioma cells to oxidative stress presenting Prxs as potential therapeutic targets.
Details
- Title: Subtitle
- Decreasing peroxiredoxin II expression decreases glutathione, alters cell cycle distribution, and sensitizes glioma cells to ionizing radiation and H2O2
- Creators
- Pameeka S. Smith-Pearson - Wake Forest UniversityMitra Kooshki - Wake Forest UniversityDouglas R. Spitz - University of IowaLeslie B. Poole - Wake Forest UniversityWeiling Zhao - Wake Forest UniversityMike E. Robbins - Wake Forest University
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.45(8), pp.1178-1189
- DOI
- 10.1016/j.freeradbiomed.2008.07.015
- PMID
- 18718523
- PMCID
- PMC2628750
- NLM abbreviation
- Free Radic Biol Med
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Language
- English
- Date published
- 07/27/2008
- Academic Unit
- Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984312979302771
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