Biphenyl-induced cytotoxicity is mediated by an increase in intracellular Zn2+
Biphenyl-induced cytotoxicity is mediated by an increase in intracellular Zn2+
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联苯诱导的细胞毒性是通过细胞内 Zn2 的增加介导的
DOI：
10.1080/01480545.2018.1499771
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发表时间：
2018
影响因子：
2.6
通讯作者：
Kamemura Norio
中科院分区：
文献类型：
--
作者：
Ae Masamichi;Imura Naohiro;Inubushi Tomoko;Abe Shin;Yusuke Bekki;Sugimoto Mayumi;Kamemura Norio
联苯在天然和人工来源中都有发现，并被用作柑橘类水果包装中的抑菌剂。人们观察到，急性接触高浓度联苯会对皮肤造成刺激，并对肝脏和肾脏产生毒性影响。然而，联苯诱导细胞毒性的机制还不是很清楚。在本研究中，用荧光探针的流式细胞术研究了联苯的细胞毒性。联苯在100 μM作用3 h后可显著增加大鼠胸腺细胞的致死率。此外，联苯在100 μM或更高时，细胞内锌离子水平升高。胞内和胞外锌离子螯合剂N，N，N‘，N’-四(2-吡啶甲基)乙二胺(TPEN)可减弱联苯引起的细胞内锌离子浓度升高和细胞死亡，但膜不通透性锌离子螯合剂N，N，N‘，N“，N”-五乙酸二乙三胺(DTPA)不能减弱联苯引起的细胞内锌离子浓度升高和细胞死亡。这些结果表明，联苯诱导的细胞毒性引起细胞内锌离子水平的增加，这种增加依赖于细胞内的锌离子。此外，联苯导致对氧化应激的敏感性增加，而TPEN抑制了联苯诱导的这种增加。我们的发现表明，联苯导致细胞内游离锌离子浓度增加，诱导细胞毒性，细胞死亡，并增加对氧化应激的敏感性。
Biphenyl is found both in natural and anthropogenic sources and is used as a fungistat in the packaging of citrus fruits. Acute exposure to high levels of biphenyl has been observed to cause skin irritation and toxic effects on the liver and kidneys. However, the mechanisms of cytotoxicity induced by biphenyl are not yet well understood. In the present study, the cytotoxicity of biphenyl was studied by flow cytometry with fluorescent probes. Biphenyl at 100 μM significantly increased cell lethality after 3 h in rat thymocytes. In addition, biphenyl at 100 μM or more elevated intracellular Zn2+levels. N,N,N′,N′-Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), an intracellular and extracellular Zn2+chelator, but not diethylenetriamine-N,N,N′,N″,N″-pentaacetic acid (DTPA), a membrane-impermeable Zn2+chelator, attenuated the biphenyl-induced increase in intracellular Zn2+levels and cell death. These results suggested that biphenyl-induced cytotoxicity caused an increase in intracellular Zn2+levels, which was dependent on internal Zn2+. Moreover, biphenyl led to an increase in sensitivity to oxidative stress, while TPEN inhibited this biphenyl-induced increase. Our findings revealed that biphenyl caused an increase in the intracellular free Zn2+concentration, inducing cytotoxicity, cell death, and an increase in sensitivity to oxidative stress.
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影响因子：
3.7
作者：
Anderson,GD;Levy,RH
通讯作者：
Levy,RH
一种用于测量完整细胞的综合联苯代谢的高效液相色谱测定法：其在大鼠肝脏以及人类肝脏和肾脏中的应用。
影响因子：
2.9
作者：
Powis,G;Moore,DJ;Wilke,TJ;Santone,KS
通讯作者：
Santone,KS
DOI：
10.1111/j.1600-0773.1976.tb03194.x
发表时间：
2009
期刊：
Pharmacology & Toxicology
影响因子：
--
作者：
T. Meyer;J. C. Larsen;E. V. Hansen;R. R. Scheline
通讯作者：
R. R. Scheline
金属硫蛋白和锌作为培养肝细胞中自由基诱导的脂质过氧化的潜在抗氧化剂。
DOI：
10.1016/s0946-672x(96)80016-2
发表时间：
1996
期刊：
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements
影响因子：
--
作者：
A. Markant;J. Pallauf
通讯作者：
J. Pallauf
影响因子：
3.5
作者：
M. N. D'errico;G. De Tullio;M. Di Gioacchino;P. Lovreglio;A. Basso;I. Drago;R. Serra;P. Apostoli;A. Vacca;L. Soleo
通讯作者：
L. Soleo