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Paraquat Inhibits Autophagy Via Intensifying the Interaction Between HMGB1 and α-Synuclein

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Abstract

Paraquat, a widely used herbicide, is associated with an increased risk of Parkinson’s disease (PD). PQ induces upregulation and accumulation of α-synuclein in neurons, which is one of the major pathological hallmarks of PD. Autophagy, as the major mechanism for the clearance of α-synuclein, is disrupted upon pesticide exposure as well as in PD patients. Meanwhile, HMGB1 is involved in autophagy dysfunction and particularly relevant to PD. However, whether PQ exposure affects HMGB1, α-synuclein, and autophagy function have rarely been reported. In this study, we found that PQ exposure impaired autophagy function via disturbing the complex formation of HMGB1 and Beclin1. Moreover, the expression of α-synuclein is modulated by HMGB1 and the interaction between HMGB1 and α-synuclein was intensified by PQ exposure. Taken together, our results revealed that HMGB1-mediated α-synuclein accumulation could competitively perturb the complex formation of HMGB1 and Beclin1, thereby inhibiting the autophagy function in SH-SY5Y cells.

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The data that support the findings of this study are available from the authors upon reasonable request.

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Funding

The present study was supported by the Ningxia Natural Science Foundation (2020AAC02018), “Light of the West” talent training program (XAB2020YW14), and Ministry of education “Chunhui plan” cooperative scientific research (Z2016059).

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  1. Kaidong Wang and Baofu Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Occupational and Environmental Health, School of Public Health and Management, Ningxia Medical University, Yinchuan City, China

    Kaidong Wang, Baofu Zhang, Binyang Zhang, Kexin Wu, Tian Tian, Weiguang Yan & Min Huang

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  1. Kaidong Wang
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  2. Baofu Zhang
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  3. Binyang Zhang
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  4. Kexin Wu
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  5. Tian Tian
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  6. Weiguang Yan
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  7. Min Huang
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Contributions

K.W., Bao.Z., Bin.Z., and K.W. did the experiments. K.W. and Bao.Z. analyzed the data. T.T. and W.Y. maintained the cell line. M.H. and K.W. designed the experiments and wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Min Huang.

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Wang, K., Zhang, B., Zhang, B. et al. Paraquat Inhibits Autophagy Via Intensifying the Interaction Between HMGB1 and α-Synuclein. Neurotox Res 40, 520–529 (2022). https://doi.org/10.1007/s12640-022-00490-x

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  • DOI: https://doi.org/10.1007/s12640-022-00490-x

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