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Action of the insecticide cyfluthrin on Ca2+ signal transduction and cytotoxicity in human osteosarcoma cells.
Human & Experimental Toxicology ( IF 2.7 ) Pub Date : 2020-04-21 , DOI: 10.1177/0960327120918298
Y-C Lu 1 , W-Z Liang 2, 3 , C-C Kuo 4 , L-J Hao 5, 6 , C-T Chou 7, 8 , C-R Jan 2
Affiliation  

Cyfluthrin is a pyrethroid insecticide and common household pesticide. The effect of cyfluthrin on Ca2+-related physiology in human osteosarcoma is unclear. This study investigated the effect of cyfluthrin on cytosolic-free Ca2+ concentrations ([Ca2+]i) and viability in MG63 human osteosarcoma cells. Cyfluthrin concentration-dependently induced [Ca2+]i rises. Cyfluthrin-induced Ca2+ entry was confirmed by the Mn2+-induced quench of fura-2 fluorescence. Cyfluthrin at concentrations of 10-100 μM induced [Ca2+]i rises. Ca2+ removal reduced the signal by approximately 50%. Cyfluthrin (100 μM) induced Mn2+ influx suggesting Ca2+ entry. Cyfluthrin-induced Ca2+ entry was inhibited 50% by protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate) and inhibitor (GF109203X) and also by three inhibitors of store-operated Ca2+ channels: nifedipine, econazole, and SKF96365. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin (TG) completely inhibited cyfluthrin-evoked [Ca2+]i rises. Conversely, treatment with cyfluthrin abolished TG-evoked [Ca2+]i rises. Inhibition of phospholipase C (PLC) with 1-[6-[((17β)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dion abolished cyfluthrin-induced [Ca2+]i rises. Cyfluthrin at 25-65 μM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester. Together, in MG63 cells, cyfluthrin induced [Ca2+]i rises by evoking PLC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca2+ entry. Cyfluthrin also caused Ca2+-independent cell death.

中文翻译:

杀虫剂氟氟氰菊酯对人骨肉瘤细胞中Ca2 +信号转导和细胞毒性的作用。

氟氟氰菊酯是拟除虫菊酯类杀虫剂,是家庭常用农药。氟氰菊酯对人骨肉瘤中Ca2 +相关生理的影响尚不清楚。这项研究调查了氟氯氰菊酯对MG63人骨肉瘤细胞中无胞质Ca2 +浓度([Ca2 +] i)和生存力的影响。氟氟氰菊酯浓度依赖性诱导的[Ca2 +] i升高。通过Mn2 +诱导的fura-2荧光猝灭证实了氟氯氰菊酯诱导的Ca2 +进入。浓度为10-100μM的氟氰菊酯诱导的[Ca2 +] i升高。去除Ca2 +可使信号降低约50%。Cyfluthrin(100μM)诱导Mn2 +流入,提示Ca2 +进入。通过蛋白激酶C(PKC)激活剂(佛波12-肉豆蔻酸酯13-乙酸酯)和抑制剂(GF109203X),以及三种由存储操作的Ca2 +通道的抑制剂,来氟氰菊酯诱导的Ca2 +进入被抑制50%:硝苯地平,益康唑和SKF96365。在不含Ca2 +的培养基中,用内质网Ca2 +泵抑制剂毒胡萝卜素(TG)完全抑制了氟氯氰菊酯诱发的[Ca2 +] i的升高。相反,用氟氯氰菊酯消除了TG诱发的[Ca2 +] i的治疗增加了。用1- [6-[(((17β)-3-methoxyestra-1,3,5 [10] -trien-17-yl)amino] hexyl] -1H-pyrrole-2,5抑制磷脂酶C(PLC)离子消除了氟氰菊酯诱导的[Ca2 +] i升高。25-65μM的氟氟氰菊酯降低了细胞活力,通过用Ca2 +螯合剂1,2-双(2-氨基苯氧基)乙烷-N,N,N',N'-四乙酸-乙酰氧基甲基酯进行预处理并不能逆转细胞活力。在一起,在MG63细胞中,氟氯氰菊酯诱导的[Ca2 +] i通过引起内质网PLC依赖的Ca2 +释放以及通过PKC敏感的存储操纵性Ca2 +进入Ca2 +进入而升高。氟氟氰菊酯还引起不依赖Ca2 +的细胞死亡。
更新日期:2020-04-21
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