Time-course of hypericin phototoxicity and effect on mitochondrial energies in EMT6 mouse mammary carcinoma cells
Time-course of hypericin phototoxicity and effect on mitochondrial energies in EMT6 mouse mammary carcinoma cells
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DOI：
10.1016/s0891-5849(98)00052-5
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发表时间：
1998-07-15
影响因子：
7.4
通讯作者：
Pardini, RS
中科院分区：
文献类型：
--
作者：
Johnson, SAS;Dalton, AE;Pardini, RS
光活化金丝桃素产生单线态氧和超氧阴离子自由基，然而，细胞内的事件有助于毒性是未知的。氧依赖性金丝桃素对EMT 6细胞的光毒性的克隆形成试验先前已经表明，0.5 μ M金丝桃素+1.5 J cm（-2）荧光灯是无毒的，而1.0 μ M金丝桃素+1.5 J cm（-2）荧光灯产生LD 40毒性。在这些剂量下发现了导致毒性的细胞内事件。乳酸脱氢酶泄漏升高为0.5 μ M和1.0 μ M金丝桃素+光照射后立即。虽然0.5 μ M金丝桃素+光的值最终恢复到对照水平，但1.0 μ M金丝桃素的渗漏随时间增加，分别表明可逆和不可逆的毒性。辐照后立即测量脂质和蛋白质氧化的增加;然而，两种剂量的这些参数均在0.5 h内恢复至对照水平。对于1.0 μ M金丝桃素+光，总细胞ATP水平和细胞呼吸均被抑制约50%的对照值。对于0.5 μ M金丝桃素+光，这些值没有变化。沿着先前报道的数据表明，光激活金丝桃素可以抑制线粒体琥珀氧化酶在体外牛心线粒体，这些数据支持氧化应激引发的线粒体损伤作为金丝桃素光毒性的关键目标。(C)1998年爱思唯尔科学公司
Photoactivated hypericin produces singlet oxygen and superoxide anion radical; however, the intracellular events contributing to toxicity are unknown. Clonogenic assays of oxygen-dependent hypericin phototoxicity to EMT6 cells have previously shown that 0.5 mu M hypericin + 1.5 J cm(-2) fluorescent light is non-toxic and that 1.0 mu M hypericin + 1.5 J cm(-2) fluorescent Light produces LD40 toxicity. Intracellular events leading to toxicity were revealed at these doses. Lactate dehydrogenase leakage was elevated for both 0.5 mu M and 1.0 mu M hypericin + light immediately following irradiation. While values eventually returned to control levels for 0.5 mu M hypericin + light, leakage increased over time for 1.0 mu M hypericin indicating reversible and irreversible toxicity, respectively. Increases in lipid and protein oxidation were measured immediately following irradiation; however, these parameters return to control levels within 0.5 h for both doses. Both total cellular ATP levels and cellular respiration were depressed by approximately 50% of control values for 1.0 mu M hypericin + light. These values were unchanged for 0.5 mu M hypericin + Light. Along with previously reported data demonstrating that light-activated hypericin can inhibit mitochondial succinoxidase in beef heart mitochondria in vitro, these data support oxidative stress-initiated mitochondrial damage as a key target in hypericin phototoxicity. (C) 1998 Elsevier Science Inc.