Phospholipid hydroperoxide glutathione peroxidase protects against singlet oxygen-induced cell damage of photodynamic therapy.
Phospholipid hydroperoxide glutathione peroxidase (PhGPx) is an important enzyme in the removal of lipid hydroperoxides (LOOHs) from cell membranes. Cancer treatments such as photodynamic therapy (PDT) induce lipid peroxidation in cells as a detrimental action. The photosensitizers used produce reactive oxygen species such as singlet oxygen ((1)O(2)). Because singlet oxygen introduces lipid hydroperoxides into cell membranes, we hypothesized that PhGPx would provide protection against the oxidative stress of singlet oxygen and therefore could interfere with cancer treatment. To test this hypothesis, human breast cancer cells (MCF-7) were stably transfected with PhGPx cDNA. Four clones with varying levels of PhGPx activity were isolated. The activities of other cellular antioxidant enzymes were not influenced by the overexpression of PhGPx. Cellular PhGPx activity had a remarkable inverse linear correlation to the removal of lipid hydroperoxides in living cells (r = -0.85), and correlated positively with cell survival after singlet oxygen exposure (r = 0.94). These data demonstrate that PhGPx provides significant protection against singlet oxygen-generated lipid peroxidation via removal of LOOH and suggest that LOOHs are major mediators in this cell injury process. Thus, PhGPx activity could contribute to the resistance of tumor cells to PDT.
Wang
H P
HP
Free Radical and Radiation Biology Program, Department of Radiology, College of Medicine, The University of Iowa, Iowa City, 52242-1101, USA
Qian
S Y
SY
Schafer
F Q
FQ
Domann
F E
FE
Oberley
L W
LW
Buettner
G R
GR
D015152:Blotting, Northern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D017323:Dihematoporphyrin Ether / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005434:Flow Cytometry; D005609:Free Radicals / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D010778:Photochemotherapy / Q000009:adverse effects*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D026082:Singlet Oxygen; D014162:Transfection; D014407:Tumor Cells, Cultured
D005609:Free Radicals; D008054:Lipid Peroxides; D012333:RNA, Messenger; D026082:Singlet Oxygen; D017323:Dihematoporphyrin Ether; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; D010100:Oxygen