A role for hydrogen peroxide in the pro-apoptotic effects of photodynamic therapy.
A role for hydrogen peroxide in the pro-apoptotic effects of photodynamic therapy.
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DOI：
10.1111/j.1751-1097.2009.00589.x
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发表时间：
2009-11
影响因子：
3.3
通讯作者：
Kessel D
中科院分区：
文献类型：
--
作者：
Price M;Terlecky SR;Kessel D
虽然在光敏细胞照射过程中形成的第一个活性氧物种(ROS)几乎总是单分子氧(1O2)，但其他ROS也与光动力疗法(PDT)的光毒效应有关。其中包括超氧阴离子自由基(·O2−)、过氧化氢(H2O2)和羟基自由基(·OH)。在这项研究中，我们研究了过氧化氢在小鼠白血病P388细胞对光动力的促凋亡反应中的作用。细胞内过氧化氢解毒的主要途径是过氧化氢酶。3-氨基-1，2，4-三氮唑抑制过氧化氢酶活性导致细胞凋亡反应增强。外源重组过氧化氢酶类似物(CAT-SKL)的加入可以减弱PDT诱导的细胞凋亡，这种类似物是专门设计用来进入细胞并更有效地定位在过氧化物体中。加入2，2‘-联吡啶也有类似的效果，2，2’-联吡啶可以螯合Fe2+，这是Fenton反应中的一个辅助因素，导致H_2O_2转化为·OH。这些结果为光敏细胞照射过程中过氧化氢的形成提供了证据，有助于光敏细胞的光动力效应。
Although the first reactive oxygen species (ROS) formed during irradiation of photosensitized cells is almost invariably singlet molecular oxygen (1O2), other ROS have been implicated in the phototoxic effects of photodynamic therapy (PDT). Among these are superoxide anion radical (•O2 −), hydrogen peroxide (H2O2) and hydroxyl radical (•OH). In this study, we investigated the role of H2O2 in the pro-apoptotic response to PDT in murine leukemia P388 cells. A primary route for detoxification of cellular H2O2 involves the peroxisomal enzyme catalase. Inhibition of catalase activity by 3-amino-1,2,4-triazole led to an increased apoptotic response. PDT-induced apoptosis was impaired by addition of an exogenous recombinant catalase analog (CAT-skl) that was specifically designed to enter cells and more efficiently localize in peroxisomes. A similar effect was observed upon addition of 2,2′-bipyridine, a reagent that can chelate Fe+2, a co-factor in the Fenton reaction that results in the conversion of H2O2 to •OH. These results provide evidence that formation of H2O2 during irradiation of photosensitized cells contributes to PDT efficacy.
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