Khat (Catha edulis) generates reactive oxygen species and promotes hepatic cell apoptosis via MAPK activation
Khat (Catha edulis) generates reactive oxygen species and promotes hepatic cell apoptosis via MAPK activation
复制标题
卡塔叶 (Catha edulis) 产生活性氧并通过 MAPK 激活促进肝细胞凋亡
DOI：
10.3892/ijmm.2013.1394
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发表时间：
2013-08-01
影响因子：
5.4
通讯作者：
Gong, Feili
中科院分区：
文献类型：
--
作者：
Abid, Morad Dirhem Naji;Chen, Juan;Gong, Feili
许多研究表明，咀嚼阿拉伯茶与急性肝脏病变或慢性肝脏疾病之间存在关联。然而，关于阿拉伯茶对肝细胞的影响知之甚少。在目前的研究中，我们研究了阿拉伯茶诱导L02人肝细胞系凋亡的机制。我们采用细胞生长抑制试验、流式细胞术和Hoechst 33258染色法检测阿茶诱导的肝细胞凋亡。Western blot检测caspase-8、-9、Bax、Bcl-2的表达水平。我们还测量了活性氧的产生。结果表明，阿拉伯茶可诱导L02细胞发生明显的肝细胞凋亡。我们发现，阿拉伯茶激活caspase-8和-9，上调Bax蛋白表达，下调Bcl-2表达水平，导致凋亡信号的协调。Khat诱导的肝细胞凋亡主要通过持续激活c-Jun NH 2-末端激酶（JNK）途径进行调节，仅部分通过细胞外信号调节激酶（ERK）级联。此外，khat诱导的活性氧（ROS）的产生和活性氧清除剂，N-乙酰-L-半胱氨酸（NAC）的激活，减弱了khat诱导的JNK和ERK的激活。我们的研究结果表明，阿拉伯茶触发细胞内ROS的产生，并依次诱导JNK的可持续激活，这反过来又导致细胞活力下降和细胞凋亡增加。
A number of studies have suggested an association between khat (Catha edulis) chewing and acute liver lesions or chronic liver disease. However, little is known about the effects of khat on hepatic cells. In the current study, we investigated the mechanism behind khat-induced apoptosis in the L02 human hepatic cell line. We used cell growth inhibition assay, flow cytometry and Hoechst 33258 staining to measure hepatocyte apoptosis induced by khat. Western blot analysis was used to detect the expression levels of caspase-8 and -9, as well as those of Bax and Bcl-2. We also measured reactive oxygen species production. The results indicated that khat induced significant hepatocyte apoptosis in L02 cells. We found that khat activated caspase-8 and -9, upregulated Bax protein expression and downregulated Bcl-2 expression levels, which resulted in the coordination of apoptotic signals. Khat-induced hepatocyte apoptosis is primarily regulated through the sustained activation of the c-Jun NH2-terminal kinase (JNK) pathway and only partially via the extracellular signal-regulated kinase (ERK) cascade. Furthermore, the khat-induced reactive oxygen species (ROS) production and the activation of the ROS scavenger, N-acetyl-L-cysteine (NAC), attenuated the khat-induced activation of JNK and ERK. Our results demonstrate that khat triggers the generation of intracellular ROS and sequentially induces the sustainable activation of JNK, which in turn results in a decrease in cell viability and an increase in cell apoptosis.