Permethrin, a pyrethroid insecticide, regulates ERK1/2 activation through membrane depolarization-mediated pathway in HepG2 hepatocytes.
Permethrin, a pyrethroid insecticide, regulates ERK1/2 activation through membrane depolarization-mediated pathway in HepG2 hepatocytes.
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DOI：
10.1016/j.fct.2018.09.009
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发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
Park Y
中科院分区：
文献类型：
--
作者：
Yang JS;Symington S;Clark JM;Park Y
氯菊酯是一种拟除虫菊酯杀虫剂，通过膜去极化起作用，已知会破坏神经元中的钙水平。钙稳态的破坏与氧化应激以及许多其他细胞功能失调有关，据报道，在动物和哺乳动物细胞模型中，氯菊酯会破坏脂质和葡萄糖代谢。然而，目前尚不清楚氯菊酯是否会影响肝细胞中的钙水平及其相关的细胞机制。因此，本研究的目的是研究氯菊酯对钙介导的细胞信号通路的影响机制，特别是对人肝细胞HepG2细胞外信号相关激酶（ERK1/2或p42/p44）的激活。目前的研究结果表明，氯菊酯处理诱导了ERK1/2的氧化应激和磷酸化，这依赖于电压敏感钠通道（VSSC）。进一步确定氯菊酯诱导的ERK1/2激活是通过代谢性谷氨酸受体(mGluRs)-磷酸肌肽磷脂酶C (PLC)-蛋白激酶C （PKC）途径介导的，而不是通过细胞内钙的改变或内质网应激介导的机制。
Permethrin is a pyrethroid insecticide that acts thru membrane depolarization and is known to disrupt calcium levels in neurons. Disrupted calcium homeostasis is linked to oxidative stress as well as many other cellular mis-functions and permethrin has been reported to disrupt lipid and glucose metabolism in animals and mammalian cell models. It is not known, however, if permethrin influences calcium levels and its associated cellular mechanisms in liver cells. Thus, the goal of the current study was to investigate the mechanisms of permethrin on calcium-mediated cellular signaling pathway, particularly on activation of extracellular signal-related kinase (ERK1/2 or p42/p44) using human hepatocytes, HepG2. The current results showed that permethrin treatment induced oxidative stress and phosphorylation of ERK1/2, which were dependent upon voltage-sensitive sodium channels (VSSC). It was further determined that permethrin-induced ERK1/2 activation was mediated by the metabotropic glutamate receptors (mGluRs)-phosphoinositide phospholipase C (PLC)-protein kinase C (PKC) pathway, but not by changes of intracellular calcium or ER stress-mediated mechanisms.
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