文献类型：期刊文献

英文题名：Cytotoxicity of CdTe quantum dots in human umbilical vein endothelial cells: the involvement of cellular uptake and induction of pro-apoptotic endoplasmic reticulum stress

作者：Yan, Ming[1];Zhang, Yun[2];Qin, Haiyan[3];Liu, Kezhou[1];Guo, Miao[1];Ge, Yakun[1];Xu, Mingen[1];Sun, Yonghong[4];Zheng, Xiaoxiang[4]

机构：[1]Hangzhou Dianzi Univ, Coll Life Informat Sci & Instrument Engn, Dept Biomed Engn, 2nd Ave 1158, Hangzhou 310018, Peoples R China;[2]Shaoxing Univ, Coll Med, Basic Med Sci, Shaoxing, Peoples R China;[3]Zhejiang Univ, Dept Chem, Hangzhou 310003, Zhejiang, Peoples R China;[4]Zhejiang Univ, Dept Biomed Engn, Zhejiang Prov Key Lab Cardiocerebral Vasc Detect, Hangzhou 310003, Zhejiang, Peoples R China

年份：2016

卷号：11

起止页码：529

外文期刊名：INTERNATIONAL JOURNAL OF NANOMEDICINE

收录：SCI-EXPANDED(收录号：WOS:000369048500001)、、Scopus(收录号：2-s2.0-84957548708)、WOS

基金：The work was supported by Zhejiang Provincial Natural Science Foundation (No.'s LY15H180012, LY13H060003, LY14C100004, and LY13C100003) and National Natural Science Foundation of China (No. 30900301).

语种：英文

外文关键词：quantum dots; human umbilical vein endothelial cells; endocytosis; ER stress; apoptosis

外文摘要：Cadmium telluride quantum dots (CdTe QDs) have been proposed to induce oxidative stress, which plays a crucial role in CdTe QDs-mediated mitochondrial-dependent apoptosis in human umbilical vein endothelial cells (HUVECs). However, the direct interactions of CdTe QDs with HUVECs and their potential impairment of other organelles like endoplasmic reticulum (ER) in HUVECs are poorly understood. In this study, we reported that the negatively charged CdTe QDs (-21.63 +/- 0.91 mV), with good dispersity and fluorescence stability, were rapidly internalized via endocytosis by HUVECs, as the notable internalization could be inhibited up to 95.52% by energy depletion (NaN3/deoxyglucose or low temperature). The endocytosis inhibitors (methyl-beta-cyclodextrin, genistein, sucrose, chlorpromazine, and colchicine) dramatically decreased the uptake of CdTe QDs by HUVECs, suggesting that both caveolae/raft- and clathrin-mediated endocytosis were involved in the endothelial uptake of CdTe QDs. Using immunocytochemistry, a striking overlap of the internalized CdTe QDs and ER marker was observed, which indicates that QDs may be transported to ER. The CdTe QDs also caused remarkable ER stress responses in HUVECs, confirmed by significant dilatation of ER cisternae, upregulation of ER stress markers GRP78/GRP94, and activation of protein kinase RNA-like ER kinase-eIF2 alpha-activating transcription factor 4 pathway (including phosphorylation of both protein kinase RNA-like ER kinase and eIF2 alpha and elevated level of activating transcription factor 4). CdTe QDs further promoted an increased C/EBP homologous protein expression, phosphorylation of c-JUN NH2-terminal kinase, and cleavage of ER-resident caspase-4, while the specific inhibitor (SP600125, Z-LEVD-fmk, or salubrinal) significantly attenuated QDs-triggered apoptosis, indicating that all three ER stress-mediated apoptosis pathways were activated and the direct participation of ER in the CdTe QDs-caused apoptotic cell death in HUVECs. Our findings provide important new insights into QDs toxicity and reveal potential cardiovascular risks for the future applications of QDs.