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Co(ii)-based metal-organic framework induces apoptosis through activating the HIF-1 alpha/BNIP3 signaling pathway in microglial cells
Yan, Xueting; Yang, Qundi; Fang, Xiaolong; Xiong, Ping; Liu, Shuang; Cao, Zhengyu; Liao, Chunyang; Liu, Sijin; Jiang, Guibin
2021-10-14
Source PublicationENVIRONMENTAL SCIENCE-NANO
ISSN2051-8153
Volume8Issue:10Pages:2866-2882
AbstractMetal-organic frameworks (MOFs) are an emerging class of porous hybrid materials constructed by coordination of metal clusters with organic ligands, and have attracted tremendous attention due to their superior properties. Although nanoscaled MOFs have been increasingly developed for bioapplications, little is known about their toxicity and potential health risks. In this study, we demonstrated that a typical cobalt-based MOF (ZIF-67) induced apoptosis in microglial cells, through activating the hypoxia-inducible factor-1 alpha (HIF-1 alpha)/BCL-2 19-kDa interacting protein 3 (BNIP3) signaling pathway. Combined cellular assays and transcriptomic analysis confirmed that ZIF-67 was able to imitate hypoxia in vitro, induced the generation of reactive oxygen species (ROS), enhanced the expression of HIF-1 alpha and BNIP3, and eventually led to apoptosis. The inflammatory process and element dyshomeostasis in microglial cells also appeared to be associated with ZIF-67 exposure. The released Co2+ from ZIF-67 could not solely explain the specific neurotoxicity of ZIF-67, since ZIF-67 generally exhibited higher toxicity than commensurable Co2+. The neurotoxicity of ZIF-67 and its underlying mechanism were further verified in vivo. These results provided not only mechanistic insights into the neurotoxicity of ZIF-67, i.e., ROS-induced apoptosis through activating the HIF-1 alpha/BNIP3 signaling pathway, but also comprehensive data, such as oxidative stress, homeostasis, and gene transcription, for environmental risk assessment of MOFs' impact on organisms.
Department环境化学与生态毒理学国家重点实验室
WOS Research AreaChemistry, Multidisciplinary ; Environmental Sciences ; Nanoscience & Nanotechnology
Document Type期刊论文
Identifierhttps://ir.rcees.ac.cn/handle/311016/45687
Collection环境化学与生态毒理学国家重点实验室
Affiliation1.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China
2.Univ Chinese Acad Sci, Coll Resources & Environm, Beijing 100049, Peoples R China
3.China Pharmaceut Univ, Sch Tradit Chinese Pharm, State Key Lab Nat Med, Nanjing 211198, Jiangsu, Peoples R China
4.China Pharmaceut Univ, Sch Tradit Chinese Pharm, Dept TCM Pharmacol, Nanjing 211198, Jiangsu, Peoples R China
Recommended Citation
GB/T 7714
Yan, Xueting,Yang, Qundi,Fang, Xiaolong,et al. Co(ii)-based metal-organic framework induces apoptosis through activating the HIF-1 alpha/BNIP3 signaling pathway in microglial cells[J]. ENVIRONMENTAL SCIENCE-NANO,2021,8(10):2866-2882.
APA Yan, Xueting.,Yang, Qundi.,Fang, Xiaolong.,Xiong, Ping.,Liu, Shuang.,...&Jiang, Guibin.(2021).Co(ii)-based metal-organic framework induces apoptosis through activating the HIF-1 alpha/BNIP3 signaling pathway in microglial cells.ENVIRONMENTAL SCIENCE-NANO,8(10),2866-2882.
MLA Yan, Xueting,et al."Co(ii)-based metal-organic framework induces apoptosis through activating the HIF-1 alpha/BNIP3 signaling pathway in microglial cells".ENVIRONMENTAL SCIENCE-NANO 8.10(2021):2866-2882.
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