Size-dependent effects of tungsten carbide-cobalt particles on oxygen radical production and activation of cell signaling pathways in murine epidermal cells
Size-dependent effects of tungsten carbide-cobalt particles on oxygen radical production and activation of cell signaling pathways in murine epidermal cells
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DOI：
10.1016/j.taap.2009.09.004
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发表时间：
2009-12-15
影响因子：
3.8
通讯作者：
Shvedova, A. A.
中科院分区：
文献类型：
--
作者：
Ding, M.;Kisin, E. R.;Shvedova, A. A.
硬质合金或硬质合金由碳化钨（WC）（85%）和金属钴（Co）（5-15%）的混合物组成。WC-Co被认为对人类具有潜在致癌性。然而，迄今为止还没有纳米尺寸WC-Co颗粒的不利影响的比较。在本研究中，我们比较了纳米和精细尺寸的WC-Co颗粒形成自由基的能力和激活转录因子AP-1和NF-κ B的倾向，沿着刺激小鼠表皮细胞系（JB 6 P+）中的促分裂原活化蛋白激酶（MAPK）信号通路。我们的结果表明，纳米WC-Co产生更高水平的羟基自由基，诱导更大的氧化应激，如GSH水平的降低所证明的，并且引起比细胞暴露于细WC-Co后观察到的更快的JB 6 P+细胞生长/增殖。在JB 6（+/+）细胞中，与精细WC-Co相比，纳米WC-Co更有效地激活AP-1和NF-κ B。纳米和精细尺寸的WC-Co颗粒也刺激MAPK，包括ERK、p38和JNK，其中纳米WC-Co的效力显著更高。最后，将JB 6（+/+）细胞与N-乙酰半胱氨酸共孵育降低AP-1活化和ERK、p38激酶和JNK的磷酸化，从而表明氧化应激参与了WC-Co诱导的毒性和AP-1活化。(C)2009年由Elsevier Inc.出版
Hard metal or cemented carbide consists of a mixture of tungsten carbide (WC) (85%) and metallic cobalt (Co) (5-15%). WC-Co is considered to be potentially carcinogenic to humans. However, no comparison of the adverse effects of nano-sized WC-Co particles is available to date. In the present study, we compared the ability of nano- and fine-sized WC-Co particles to form free radicals and propensity to activate the transcription factors, AP-1 and NF-kappa B, along with stimulation of mitogen-activated protein kinase (MAPK) signaling pathways in a mouse epidermal cell line (JB6 P+). Our results demonstrated that nano-WC-Co generated a higher level of hydroxyl radicals, induced greater oxidative stress, as evidenced by a decrease of GSH levels, and caused faster JB6 P+ cell growth/proliferation than observed after exposure of cells to fine WC-Co. In addition, nano-WC-Co activated AP-1 and NF-kappa B more efficiently in JB6(+/+) cells as compared to fine WC-Co. Experiments using AP-1-luciferase reporter transgenic mice confirmed the activation of AP-1 by nano-WC-Co. Nano- and fine-sized WC-Co particles also stimulated MAPKs, including ERKs, p38, and JNKs with significantly higher potency of nano-WC-Co. Finally, co-incubation of the JB6(+/+) cells with N-acetylcysteine decreased AP-1 activation and phosphorylation of ERKs, p38 kinase, and JNKs, thus suggesting that oxidative stress is involved in WC-Co-induced toxicity and AP-1 activation. (C) 2009 Published by Elsevier Inc.