CuZn-SOD suppresses the bovine papillomavirus-induced proliferation of fibroblasts.
Eukaryotic cells continuously produce reactive oxygen species (ROS) and have mechanisms to control ROS levels. ROS have been shown to mediate cell proliferation and transformation. We studied the effect of CuZn-superoxide dismutase (CuZnSOD) on the focus-forming ability of bovine papillomavirus (BPV-1) wtDNA and hypertransforming mutant of its major oncoprotein E5, E5-17S. We found that CuZnSOD suppresses the focus-forming ability of BPV-1 wtDNA and E5 oncoprotein. Significantly fewer foci were detected in pCGCuZnSOD- and BPV-1 DNA-cotransfected cell culture compare to BPV-1 DNA-transfected cell culture (p<0.001). CuZnSOD decreases the rate of cell proliferation in both non-transformed C127 and BPV-1- and E5-transformed cell lines. CuZnSOD decelerates cell entry into the S phase of the cell cycle and has a suppressing effect on the actively dividing cells. As the transformed cells proliferate faster than normal cells when confluent, CuZnSOD inhibits the growth of foci. These results indicate that superoxide radicals may be involved in signaling for cell proliferation and that SOD suppresses cell proliferation.
Rausalu
Kai
K
Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Karo-Astover
Liis
L
Kilk
Ann
A
Ustav
Mart
M
D000818:Animals; D052688:Bovine papillomavirus 1 / Q000187:drug effects* / Q000502:physiology; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects*; D002472:Cell Transformation, Viral / Q000187:drug effects*; D002478:Cells, Cultured; D004279:DNA, Viral; D005347:Fibroblasts / Q000187:drug effects / Q000821:virology*; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000187:drug effects*; D030361:Papillomavirus Infections / Q000378:metabolism / Q000821:virology; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D014162:Transfection
D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; C054304:oncogene protein E5, Bovine papillomavirus type 1; D013481:Superoxides; D013482:Superoxide Dismutase