BRCA1 down-regulates cellular levels of reactive oxygen species.
Previous studies have shown that the breast cancer suppressor BRCA1 stimulates antioxidant gene expression and protects cells against oxidative stress. To further examine this important function, we tested whether BRCA1 could modulate intracellular levels of reactive oxygen species (ROS). Wild-type BRCA1 (but not a cancer-associated mutant) significantly reduced ROS levels, determined by DCF fluorescence assays by flow cytometry and confocal microscopy. The BRCA1 and REF1 pathways for reduction of ROS levels appear to exhibit cross-talk. BRCA1 also reduced the levels of protein nitration and H(2)O(2)-induced oxidative damage to DNA. Thus, BRCA1 may protect cellular macromolecules by reducing intracellular ROS levels.
Department of Oncology, Lombardi Comprehensive Cancer Center/Georgetown University, 3970 Reservoir Road, NW, Box 571469, Washington, DC 20057-1469, USA.
Tapas
T
Saha
Jeong Keun
JK
Rih
Eliot M
EM
Rosen
D019313:BRCA1 Protein / Q000502:physiology*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D018613:Microscopy, Confocal; D018384:Oxidative Stress; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism
D019313:BRCA1 Protein; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species