The toxicity of multi-walled carbon nanotubes (MWCNTs) to human endothelial cells: The influence of diameters of MWCNTs
The toxicity of multi-walled carbon nanotubes (MWCNTs) to human endothelial cells: The influence of diameters of MWCNTs
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多壁碳纳米管（MWCNT）对人内皮细胞的毒性：MWCNT直径的影响
DOI：
10.1016/j.fct.2019.02.026
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发表时间：
2019
影响因子：
4.3
通讯作者：
Cao Yi
中科院分区：
文献类型：
--
作者：
Zhao Xuqi;Chang Shiwei;Long Jimin;Li Juan;Li Xianqiang;Cao Yi
多壁碳纳米管（MWCNTs）的生物学应用可能导致其暴露于人体血管，但其理化性质对内皮细胞毒性的影响尚不完全清楚。本研究将人脐静脉内皮细胞（HUVECs）暴露于三种市售MWCNTs，即XFM4、XFM22和XFM34（直径XFM4 < XFM22 < XFM34），以了解其直径对毒性的可能作用。在相同质量浓度下，XFM4诱导的细胞毒性水平明显高于其他两种MWCNTs，并且HUVECs内化了更多的XFM4。细胞因子释放、单核细胞粘附和细胞内活性氧水平仅在XFM4处理后才显著诱导。暴露于XFM4显著降低了自噬基因自噬相关7 （ATG7）、自噬相关12 （ATG12）和beclin 1 （BECN1）的表达，增加了内质网（ER）应激基因DNA损伤诱导转录物3 （DDIT3）和X-box结合蛋白1剪接（XBP-1s）的表达。此外，化学物质对自噬内质网应激的调节导致XFM4的细胞毒性显著增加，但对XFM34的细胞毒性影响很小。这些数据表明，MWCNTs的直径可能通过自噬功能障碍和内质网应激影响其对HUVECs的毒性。
The biological applications of multi-walled carbon nanotubes (MWCNTs) may lead to their exposure to human blood vessels, but the influence of their physicochemical properties on toxicity to endothelial cells is incompletely known. Here, human umbilical vein endothelial cells (HUVECs) were exposed to three commercially available MWCNTs, namely XFM4, XFM22, and XFM34 (diameters XFM4 < XFM22 < XFM34), to understand the possible role of their diameter on toxicity. Based on the same mass concentration, XFM4 induced significantly higher level of cytotoxicity than the other two MWCNTs, and HUVECs internalized more XFM4. Cytokine release, monocyte adhesion, and intracellular reactive oxygen species levels were significantly induced only after XFM4 treatment. The exposure to XFM4 significantly reduced the expression of autophagic genes autophagy-related 7 (ATG7), autophagy-related 12 (ATG12), and beclin 1 (BECN1) and increased the expression of endoplasmic reticulum (ER) stress genes DNA damage inducible transcript 3 (DDIT3) and X-box binding protein 1 spliced (XBP-1s). Moreover, the modulation of autophagy-ER stress by chemicals resulted in a significant increase in the cytotoxicity of XFM4 but had minimal impact on the cytotoxicity of XFM34. These data indicate that the diameter of MWCNTs may influence their toxicity to HUVECs, probably through autophagy dysfunction and ER stress.