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Diagnostic Pathology

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Open Access 01-12-2016 | Research

Beclin1 and HMGB1 ameliorate the α-synuclein-mediated autophagy inhibition in PC12 cells

Authors: Kaihua Wang, Jianmin Huang, Wei Xie, Longjian Huang, Canhua Zhong, Zhenzhen Chen

Published in: Diagnostic Pathology | Issue 1/2016

Abstract

Background

Aberrant α-synuclein aggregation due to the deficiency of ubiquitin-proteasome or of autophagy characterizes the parkinson disease (PD). High mobility group box 1 (HMGB1) is a novel stress sensor to mediate the persistent neuro-inflammation and the consequent progressive neurodegeneration, via controlling the cellular autophagy/apoptosis checkpoint during inflammation. Moreover, HMGB1 has been recently indicated to involve in the autophagic degradation of α-synuclein.

Methods

In the current study, we investigated the influence of the overexpressed α-synuclein of wild type (wt) or mutant type (A53T and A30P, mt) on the cytosolic levels of HMGB1 and Beclin1 and on the starvation-induced autophagy in pheochromocytoma PC12 cells. And then we explored the overexpression of HMGB1 or of Beclin1 on the α-synuclein degradation and on the autophagy in the α-synuclein-overexpressed PC12 cells.

Results

It was demonstrated that α-synuclein overexpression inhibited the trans-location of HMGB1 from nucleus to cytosol and reduced the cytosolic level of Beclin1 in PC12 cells, and inhibited the starvation-induced autophagy via downregulating autophagy-associated markers and via reducing the autophagic vesicles in PC12 cells under starvation. On the other side, the intracellular promotion of either HMGB1 or Beclin1 upregulated the α-synuclein degradation and ameliorated the α-synuclein-mediated autophagy reduction in PC12 cells. However, the exogenous HMGB1 treatment exerted no such regulation in PC12 cells.

Conclusion

In summary, our study confirmed the positive regulation by HMGB1 and Beclin1 on the α-synuclein degradation and on the starvation-induced autophagy in PC12 cells, implying both markers as prominent targets to promote the α-synuclein degradation.

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Title: Beclin1 and HMGB1 ameliorate the α-synuclein-mediated autophagy inhibition in PC12 cells
Authors: Kaihua Wang
Jianmin Huang
Wei Xie
Longjian Huang
Canhua Zhong
Zhenzhen Chen
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Diagnostic Pathology / Issue 1/2016
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/s13000-016-0459-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Beclin1 and HMGB1 ameliorate the α-synuclein-mediated autophagy inhibition in PC12 cells

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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