核因子-κB 信号转导介导锑诱导的星形胶质细胞激活。

Nuclear Factor-κB Signaling Mediates Antimony-induced Astrocyte Activation.

机构信息

Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019, Jiangsu, China.

Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019, Jiangsu, China;Fudan University Taizhou Institute of Health Sciences, Taizhou 225300, Jiangsu, China.

出版信息

Biomed Environ Sci. 2021 Jan 20;34(1):29-39. doi: 10.3967/bes2021.005.

DOI:10.3967/bes2021.005

PMID:33531105

Abstract

OBJECTIVE

Antimony (Sb) has recently been identified as a novel nerve poison, although the cellular and molecular mechanisms underlying its neurotoxicity remain unclear. This study aimed to assess the effects of the nuclear factor kappa B (NF-κB) signaling pathway on antimony-induced astrocyte activation.

METHODS

Protein expression levels were detected by Western blotting. Immunofluorescence, cytoplasmic and nuclear fractions separation were used to assess the distribution of p65. The expression of protein in brain tissue sections was detected by immunohistochemistry. The levels of mRNAs were detected by Quantitative real-time polymerase chain reaction (qRT-PCR) and reverse transcription-polymerase chain reaction (RT-PCR).

RESULTS

Antimony exposure triggered astrocyte proliferation and increased the expression of two critical protein markers of reactive astrogliosis, inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP), indicating that antimony induced astrocyte activation and . Antimony exposure consistently upregulated the expression of inflammatory factors. Moreover, it induced the NF-κB signaling, indicated by increased p65 phosphorylation and translocation to the nucleus. NF-κB inhibition effectively attenuated antimony-induced astrocyte activation. Furthermore, antimony phosphorylated TGF-β-activated kinase 1 (TAK1), while TAK1 inhibition alleviated antimony-induced p65 phosphorylation and subsequent astrocyte activation.

CONCLUSION

Antimony activated astrocytes by activating the NF-κB signaling pathway.

摘要

目的

最近发现锑是一种新型的神经毒物，但其神经毒性的细胞和分子机制尚不清楚。本研究旨在评估核因子 kappa B（NF-κB）信号通路对锑诱导的星形胶质细胞激活的影响。

方法

通过 Western blot 检测蛋白表达水平。免疫荧光、细胞质和核部分离用于评估 p65 的分布。免疫组织化学检测脑组织切片中蛋白的表达。通过定量实时聚合酶链反应（qRT-PCR）和逆转录聚合酶链反应（RT-PCR）检测 mRNA 水平。

结果

锑暴露触发星形胶质细胞增殖，并增加了两种反应性星形胶质细胞的关键蛋白标志物的表达，诱导型一氧化氮合酶（iNOS）和胶质纤维酸性蛋白（GFAP），表明锑诱导星形胶质细胞激活和炎症。锑暴露一致地上调了炎症因子的表达。此外，它诱导了 NF-κB 信号转导，表现为 p65 磷酸化增加和核转位。NF-κB 抑制有效地减弱了锑诱导的星形胶质细胞激活。此外，锑磷酸化 TGF-β激活激酶 1（TAK1），而 TAK1 抑制减轻了锑诱导的 p65 磷酸化和随后的星形胶质细胞激活。