Luteolin suppresses cisplatin-induced apoptosis in auditory cells: Possible mediation through induction of heme oxygenase-1 expression
Luteolin suppresses cisplatin-induced apoptosis in auditory cells: Possible mediation through induction of heme oxygenase-1 expression
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DOI：
10.1089/jmf.2007.591
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发表时间：
2008-06-01
影响因子：
2.4
通讯作者：
Kim, Bok-Ryang
中科院分区：
文献类型：
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作者：
Choi, Byung-Min;Lim, Dai-Won;Kim, Bok-Ryang
木犀草素已被证明具有抗肿瘤、抗氧化和抗炎的特性。在本研究中，我们研究了木犀草素对顺铂诱导的听觉（House Ear Institute-Organ of Corti 1 [HEI-OC1]）细胞凋亡的保护机制。木犀草素诱导血红素氧合酶-1 （HO-1）的表达呈剂量依赖性和时间依赖性。木犀草素还激活了细胞外信号调节激酶（ERK）丝裂原活化蛋白激酶途径，在HO-1的表达中起重要作用。木犀草素对顺铂诱导的细胞凋亡具有保护作用。木犀草素的保护作用被HO抑制剂锌原卟啉IX （ZnPP IX）和反义寡脱氧核苷酸所取代。此外，木犀草素预处理可以抑制caspase-3的激活和线粒体功能障碍，并且在ZnPP IX或PD098059存在时，木犀草素对caspase-3激活的影响消失。这些结果表明木犀草素通过ERK通路介导HO-1的表达，并且HO-1的激活可以抑制顺铂诱导的hei - oc11细胞凋亡。
Luteolin has been shown to possess antitumorigenic, antioxidant, and anti-inflammatory properties. In the present study, we investigated the protective mechanism of luteolin against cisplatin-induced apoptosis in auditory (House Ear Institute-Organ of Corti 1 [HEI-OC1]) cells. Luteolin was found to induce the expression of heme oxygenase-1 (HO-1) in a dose- and time-dependent manner. Luteolin also activated the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase pathway, which plays an important role in the expression of HO-1. Luteolin protected the cells against cisplatin-induced apoptotic cell death. The protective effect of luteolin was abrogated by zinc protoporphyrin IX (ZnPP IX), an HO inhibitor, and antisense oligodeoxynucleotides against the HO-1 gene. Furthermore, pretreatment with luteolin inhibited the activation of caspase-3 and the mitochondrial dysfunction, and the effect of luteolin on the activation of caspase-3 disappeared in the presence of ZnPP IX or PD098059. These results demonstrate that the expression of HO-1 by luteolin is mediated by the ERK pathway, and also that the activating of HO-1 inhibits cisplatin-induced apoptosis in HEI-OC1 1 cells.