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The anti-apoptotic effects of caspase inhibitors on propyl gallate-treated HeLa cells in relation to reactive oxygen species and glutathione levels

机译:caspase抑制剂对没食子酸丙酯处理的HeLa细胞的抗凋亡作用与活性氧和谷胱甘肽水平的关系

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摘要

Propyl gallate (PG) as a synthetic antioxidant is widely used in processed food, cosmetics and medicinal preparations. Despite the assumed low toxicity of PG, it exerts a variety of effects on tissue and cell functions. In the present study, we evaluated the anti-apoptotic effects of caspase inhibitors on PG-treated human cervix adenocarcinoma HeLa cells in relation to the changes of reactive oxygen species (ROS) and glutathione (GSH) levels. PG induced apoptosis in a dose-dependent manner, as evidenced by sub-G1 cells and annexin V staining cells. Treatment with pan-caspase inhibitor, caspase-3 inhibitor, caspase-8 inhibitor or caspase-9 inhibitor significantly prevented apoptosis in PG-treated HeLa cells at 24 h. The intracellular ROS levels including O2•− were increased or decreased in PG-treated HeLa cells depending on the incubation times (1 or 24 h). PG depleted intracellular GSH content in HeLa cells at 24 h. Treatment with caspase inhibitor reduced ROS levels and significantly prevented GSH depletion in PG-treated HeLa cells at 24 h. In conclusion, PG induced apoptosis in HeLa cells. The anti-apoptotic effect of caspase inhibitor on PG-induced HeLa cell death was closely related to the reduction of ROS levels, especially mitochondrial O2•−, as well as to the inhibition of GSH depletion.
机译:没食子酸丙酯(PG)作为合成抗氧化剂,广泛用于加工食品,化妆品和药物制剂中。尽管假定PG毒性低,但它对组织和细胞功能有多种作用。在本研究中,我们评估了胱天蛋白酶抑制剂对PG治疗的人宫颈腺癌HeLa细胞的抗凋亡作用与活性氧(ROS)和谷胱甘肽(GSH)水平的变化有关。 PG以剂量依赖性方式诱导凋亡,这由sub-G1细胞和膜联蛋白V染色细胞所证实。用泛半胱天冬酶抑制剂,半胱天冬酶3抑制剂,半胱天冬酶8抑制剂或半胱天冬酶9抑制剂处理可显着预防PG处理的HeLa细胞在24小时内的凋亡。 PG处理的HeLa细胞中的细胞内ROS水平(包括O 2 •-)根据孵育时间(1或24 h)而升高或降低。 PG在24 h耗尽HeLa细胞的细胞内GSH含量。用半胱天冬酶抑制剂治疗可降低ROS含量,并在24小时内显着阻止PG处理的HeLa细胞中GSH的消耗。总之,PG诱导HeLa细胞凋亡。 caspase抑制剂对PG诱导的HeLa细胞死亡的抗凋亡作用与ROS水平的降低密切相关,尤其是线粒体O 2 •-以及抑制谷胱甘肽耗竭。

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