Phospholipid hydroperoxide glutathione peroxidase protects against singlet oxygen-induced cell damage of photodynamic therapy
Phospholipid hydroperoxide glutathione peroxidase protects against singlet oxygen-induced cell damage of photodynamic therapy
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DOI：
10.1016/s0891-5849(01)00469-5
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发表时间：
2001-04-15
影响因子：
7.4
通讯作者：
Buettner, GR
中科院分区：
文献类型：
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作者：
Wang, HP;Qian, SY;Buettner, GR
磷脂氢过氧化物谷胱甘肽过氧化物酶（PhGPx）是细胞膜中脂质氢过氧化物（LOOHs）脱除的重要酶。癌症治疗如光动力疗法（PDT）诱导细胞脂质过氧化作为一种有害作用。所使用的光敏剂产生活性氧，如单线态氧（O-1(2)）。由于单线态氧将脂质氢过氧化物引入细胞膜，我们假设PhGPx可以提供抵抗单线态氧氧化应激的保护，从而可能干扰癌症治疗。为了验证这一假设，用PhGPx cDNA稳定转染人乳腺癌细胞（MCF-7）。分离出4个不同水平PhGPx活性的克隆。其他细胞抗氧化酶的活性不受PhGPx过表达的影响。细胞PhGPx活性与活细胞中脂质氢过氧化物的去除呈显著的负线性相关（r = -0.85），与单线态氧暴露后的细胞存活率呈正相关（r = 0.94）。这些数据表明，PhGPx通过去除LOOH对单线态氧生成的脂质过氧化具有显著的保护作用，并表明LOOH是该细胞损伤过程中的主要介质。因此，PhGPx活性可能有助于肿瘤细胞对PDT的抗性。(C) 2001爱思唯尔科学公司
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 (O-1(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. (C) 2001 Elsevier Science Inc.