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Desferrioxamine Ameliorates Lipopolysaccharide-Induced Lipocalin-2 Upregulation via Autophagy Activation in Primary Astrocytes

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Abstract

Lipocalin-2 (LCN2) is an important regulator of both neuroinflammation and iron homeostasis. Upregulated LCN2 was observed in reactive astrocytes in the Parkinson’s disease (PD) models. In the present study, we reported iron chelator deferoxamine (DFO) abolished lipopolysaccharide (LPS)-induced LCN2 upregulation in primary astrocytes, although iron overload had no effects. The suppressive effects of DFO were consistent with autophagy inducer rapamycin or carfilzomib, blocked by autophagy inhibitor 3-methyladenine rather than chloroquine or bafilomycin A1, meanwhile, while were not dependent on proteasome system and NF-κB pathway. DFO was not able to ameliorate LCN2 upregulation in α-synuclein-treated astrocytes, because DFO failed to induce autophagy in these cells. We further demonstrated that DFO could not enhance autophagy lysosomal degradation, however promoted secretory autophagy in primary astrocytes with LPS insults. These data suggest that DFO could serve as an autophagy activator, capable of ameliorating the upregulation of LCN2 in astrocytes by acting on the formation of autophagosomes and secretory autophagy. This provides better understandings of DFO-mediated neuroprotection against neuroinflammation and provides new insights that autophagy activation could be beneficial approaches in PD.

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Data Availability

All data in our study are available upon request.

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Acknowledgements

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Funding

This work was supported by the National Natural Science Foundation of China (31771124, 32170984, and 31871049), the Natural Science Foundation of Shandong Province (ZR2021MC116), the Excellent Innovative Team of Shandong Province, and the Taishan Scholars Construction Project.

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  1. Institute of Brain Science and Disease, School of Basic Medicine, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Qingdao University, Qingdao, 266071, China

    Juntao Cui, Yu Yuan, Jun Wang, Ning Song & Junxia Xie

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  1. Juntao Cui
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  2. Yu Yuan
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  3. Jun Wang
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Ning Song and Junxia Xie designed and revised the article; Juntao Cui, Yu Yuan, and Jun Wang performed the experiments and analyzed the data. Ning Song and Juntao Cui wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Ning Song or Junxia Xie.

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Cui, J., Yuan, Y., Wang, J. et al. Desferrioxamine Ameliorates Lipopolysaccharide-Induced Lipocalin-2 Upregulation via Autophagy Activation in Primary Astrocytes. Mol Neurobiol 59, 2052–2067 (2022). https://doi.org/10.1007/s12035-021-02687-1

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