TFEB-lysosome pathway activation is associated with different cell death responses to carbon quantum dots in Kupffer cells and hepatocytes

Particle and Fibre Toxicology

Mengran Yang¹  Yuanjian Zhang¹  Ting Zhang²  Ying Yao²  Yanting Pang²  Daming Wu²  Ying Ma² 

[1] Jiangsu Engineering Laboratory of Smart Carbon-Rich Materials and Devices, Jiangsu Province Hi-Tech Key Laboratory for Bio-Medical Research, School of Chemistry and Chemical Engineering, Southeast University;Key Laboratory of Environmental Medicine and Engineering, Ministry of Education, School of Public Health, Southeast University;

关键词: Hepatotoxicity;    Carbon quantum dots;    Lysosomal stress;    Autophagic flux;    TFEB pathway;   

DOI  :  10.1186/s12989-022-00474-x

来源: DOAJ

【 摘 要 】

Abstract Background Carbon dot has been widely used in biomedical field as a kind of nanomaterial with low toxicity and high biocompatibility. CDs has demonstrated its unique advantages in assisted drug delivery, target diagnosis and targeted therapy with its small size and spontaneous fluorescence. However, the potential biosafety of CDs cannot be evaluated. Therefore, we focused on the study of liver, the target organ involved in CDs metabolism, to evaluate the risk of CDs in vitro. Methods and results Liver macrophage KUP5 cells and normal liver cells AML12 cells were incubated in CDs at the same concentration for 24 h to compare the different effects under the same exposure conditions. The study found that both liver cell models showed ATP metabolism disorder, membrane damage, autophagosome formation and lysosome damage, but the difference was that, KUP5 cells exhibited more serious damage than AML12 cells, suggesting that immunogenic cell type is particularly sensitive to CDs. The underlying mechanism of CDs-induced death of the two hepatocyte types were also assessed. In KUP5 cells, death was caused by inhibition of autophagic flux caused by autophagosome accumulation, this process that was reversed when autophagosome accumulation was prevented by 3-MA. AML12 cells had no such response, suggesting that the accumulation of autophagosomes caused by CDs may be specific to macrophages. Conclusion Activation of the TFEB-lysosome pathway is important in regulating autophagy and apoptosis. The dual regulation of ERK and mTOR phosphorylation upstream of TFEB influences the death outcome of AML12 cells. These findings provide a new understanding of how CDs impact different liver cells and contribute to a more complete toxicological safety evaluation of CDs.

【 授权许可】

Unknown