Document Detail

Profiling mitochondrial proteins in radiation-induced genome-unstable cell lines with persistent oxidative stress by mass spectrometry.
MedLine Citation:
PMID:  18494543     Owner:  NLM     Status:  MEDLINE    
Previous work by Morgan and coworkers on radiation-induced genome instability in Chinese hamster ovary (CHO) cell lines showed that unstable LS-12 cells had persistently elevated levels of reactive oxygen species (ROS) that were likely due to dysfunctional mitochondria. To further investigate the correlation between radiation-induced genome instability and dysfunctional mitochondria, we performed quantitative high-throughput mass spectrometry on samples enriched in mitochondrial proteins from three chromosomally unstable CHO cell lines and their stable unirradiated GM10115 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. The LS-12 cell line, which exhibited the highest level of ROS among the three unstable cell lines, was characterized by eight significantly down-regulated mitochondrial proteins, all associated with the TCA (tricarboxylic acid). Elevated levels of ROS relative to the unirradiated parental control were also statistically significant for the CS-9 cell line. The protein profile of CS-9 revealed five significantly up-regulated mitochondrial proteins, three of which are involved in oxidative phosphorylation. Elevation of ROS in the unstable 115 cell line was nearly as large as that seen in CS-9 cells but was not statistically significant. The mitochondrial protein profile of 115 cells showed significant down-regulation of acetyl-CoA-acetyltransferase, which was also down-regulated in LS-12, and two other proteins with abundances that were significantly different from control levels but were not directly related to either the TCA or oxidative phosphorylation. These results provide further evidence that elevated ROS and mitochondrial dysfunction are associated with radiation-induced genome instability; however, additional work is required to establish a firm mechanistic relationship between these end points.
J H Miller; S Jin; W F Morgan; A Yang; Y Wan; U Aypar; J S Peters; D L Springer
Related Documents :
18427623 - Mechanisms of retinal ganglion specific-cell death in leber hereditary optic neuropathy.
22592193 - An active product of cruciferous vegetables, 3,3'-diindolylmethane, inhibits invasive p...
7634383 - Two polyamine analogs (be-4-4-4 and be-4-4-4-4) directly affect growth, survival, and c...
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Radiation research     Volume:  169     ISSN:  0033-7587     ISO Abbreviation:  Radiat. Res.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-22     Completed Date:  2008-07-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0401245     Medline TA:  Radiat Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  700-6     Citation Subset:  IM; S    
Washington State University Tri-Cities, Richland, WA, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
CHO Cells
Cell Line, Tumor
In Situ Hybridization, Fluorescence
Mass Spectrometry / methods*
Mitochondria / metabolism
Mitochondrial Proteins / metabolism*
Oxidative Stress*
Peptides / chemistry
Proteomics / methods
Reactive Oxygen Species
Reg. No./Substance:
0/Mitochondrial Proteins; 0/Peptides; 0/Reactive Oxygen Species

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Radiation-induced HPRT mutations resulting from misrejoined DNA double-strand breaks.
Next Document:  Resveratrol reduces radiation-induced chromosome aberration frequencies in mouse bone marrow cells.