Co(II)-based metal–organic framework induces apoptosis through activating the HIF-1α/BNIP3 signaling pathway in microglial cells,Environmental Science: Nano

当前位置： X-MOL 学术 › Environ. Sci.: Nano › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Co(II)-based metal–organic framework induces apoptosis through activating the HIF-1α/BNIP3 signaling pathway in microglial cells
Environmental Science: Nano ( IF 5.8 ) Pub Date : 2021-08-24 , DOI: 10.1039/d1en00719j
Xueting Yan _{1,

2} , Qundi Yang _{1,

3} , Xiaolong Fang ₁ , Ping Xiong _{1,

2} , Shuang Liu _{1,

2} , Zhengyu Cao ₃ , Chunyang Liao _{1,

2} , Sijin Liu _{1,

2} , Guibin Jiang _{1,

2}

Affiliation

Metal–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-1α (HIF-1α)/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-1α 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-1α/BNIP3 signaling pathway, but also comprehensive data, such as oxidative stress, homeostasis, and gene transcription, for environmental risk assessment of MOFs' impact on organisms.

中文翻译：

Co(II)基金属-有机骨架通过激活小胶质细胞中的HIF-1α/BNIP3信号通路诱导细胞凋亡

金属-有机骨架（MOFs）是一类新兴的多孔杂化材料，由金属簇与有机配体配位而成，由于其优异的性能而引起了极大的关注。尽管纳米级 MOF 越来越多地用于生物应用，但对其毒性和潜在的健康风险知之甚少。在这项研究中，我们证明了典型的钴基 MOF（ZIF-67）通过激活缺氧诱导因子-1α（HIF-1α）/BCL-2 19-kDa 相互作用蛋白 3（BNIP3 ) 信号通路。结合细胞检测和转录组学分析证实 ZIF-67 能够模拟体外缺氧, 诱导活性氧 (ROS) 的产生，增强 HIF-1α 和 BNIP3 的表达，最终导致细胞凋亡。小胶质细胞中的炎症过程和元素稳态失调似乎也与 ZIF-67 暴露有关。ZIF-67释放的 Co ²⁺不能单独解释 ZIF-67 的特定神经毒性，因为 ZIF-67 通常表现出比可比 Co ²⁺更高的毒性。ZIF-67的神经毒性及其潜在机制在体内得到了进一步验证。这些结果不仅提供了对 ZIF-67 神经毒性的机制见解，即, ROS 通过激活 HIF-1α/BNIP3 信号通路诱导细胞凋亡，以及综合数据，如氧化应激、稳态和基因转录，用于 MOF 对生物体影响的环境风险评估。

更新日期：2021-09-16

点击分享查看原文

点击收藏

阅读更多本刊最新论文