Profiling mitochondrial proteins in radiation-induced genome-unstable cell lines with persistent oxidative stress by mass spectrometry
Radiation-induced genome instability (RIGI) is a response to radiation exposure in which the progeny of surviving cells exhibit increased frequency of chromosomal changes many generations after the initial insult. Persistently elevated oxidative stress accompanying RIGI and the ability of free-radical scavengers, given before irradiation, to reduce the incidence of instability suggest that radiation induced alterations to mitochondrial function likely play a role in RIGI. To further elucidate this mechanism, we performed high-throughput quantitative mass spectrometry on samples enriched in mitochondrial proteins from three chromosomally-unstable GM10115 Chinese-hamster-ovary cell lines and their stable parental cell line. Out of several hundred identified proteins, sufficient data were collected on 74 mitochondrial proteins to test for statistically significant differences in their abundance between unstable and stable cell lines. Each of the unstable cell lines showed a distinct profile of statistically-significant differential abundant mitochondrial proteins. The LS-12 cell line was characterized by 8 downregulated proteins, whereas the CS-9 cell line exhibited 5 distinct up-regulated proteins. The unstable 115 cell line had two down-regulated proteins, one of which was also downregulated in LS-12, and one up-regulated protein relative to stable parental cells. The mitochondrial protein profiles for LS-12 and C-9 provide further evidence that mitochondrial dysfunction is involved in the genome instability of these cell lines.
- Research Organization:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 947911
- Report Number(s):
- PNNL-SA-56595; RAREAE; KP1501030; TRN: US200905%%306
- Journal Information:
- Radiation Research, 169(6):700-706, Vol. 169, Issue 6; ISSN 0033-7587
- Country of Publication:
- United States
- Language:
- English
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