Hematoporphyrin monomethyl ether photodynamic damage on HeLa cells by means of reactive oxygen species production and cytosolic free calcium concentration elevation
Hematoporphyrin monomethyl ether photodynamic damage on HeLa cells by means of reactive oxygen species production and cytosolic free calcium concentration elevation
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DOI：
10.1016/j.canlet.2004.07.005
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发表时间：
2004-12-08
期刊：
影响因子：
9.7
通讯作者：
Li, ZS
中科院分区：
文献类型：
--
作者：
Ding, XM;Xu, QZ;Li, ZS
血卟啉单甲醚（HMME）是一种新型的卟啉类光敏剂，在光动力学治疗（PDT）中具有广阔的应用前景。在HeLa细胞中研究HMME-PDT诱导的细胞死亡及其机制。我们证明HMME-PDT可以通过坏死和凋亡诱导细胞死亡。单重态氧猝灭剂叠氮化钠和羟基自由基清除剂D-甘露醇对HMME-PDT诱导的HeLa细胞凋亡和坏死均有保护作用，表明活性氧（ROS）如单重态氧和羟基自由基在HMME-PDT诱导的HeLa细胞死亡中起决定性作用。叠氮化钠或D-甘露醇也抑制HMME-PDT介导的[Ca 2 +]（i）升高。细胞内钙离子螯合剂BAPTA/AM可抑制HMME-PDT后细胞色素C（Cyto C）从线粒体释放到胞浆中以及Caspase-3的激活。这些结果表明，HMME-PDT诱导的HeLa细胞凋亡产生的ROS可能是通过[Ca 2 +]（i）升高介导Cyto C释放和Caspase-3活化，并启动随后的凋亡晚期阶段。出版社：Elsevier爱尔兰Ltd.
Hematoporphyrin monomethyl ether (HMME) is a novel and promising porphyrin-related photosensitizer for photodynamic therapy (PDT). HMME-PDT-induced cell death and its mechanisms were investigated in HeLa cells. We demonstrated that HMME-PDT could induce cell death through both necrosis and apoptosis. Sodium azide (the singlet oxygen quencher) or D-mannitol (the hydroxyl radical scavenger) could protect HeLa cells from the apoptosis and necrosis induced by HMME-PDT, showing that reactive oxygen species (ROS), such as singlet oxygen and hydroxyl radical, played a decisive role in HMME-PDT-induced HeLa cells death. Sodium azide or D-mannitol also inhibited HMME-PDT-mediated [Ca2+](i) elevation. Cytochrome C (Cyto C) release from mitochondria into cytosol and Caspase-3 activation after HMME-PDT were inhibited by BAPTA/AM (an intracellular calcium chelator). These results demonstrated that ROS generated in HeLa cells by HMME-PDT-induced apoptosis may be through [Ca2+](i) elevation which mediates Cyto C release and Caspase-3 activition and initiates the subsequent late stages of apoptosis. Published by Elsevier Ireland Ltd.