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Issue 26, 2019, Issue in Progress
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PKM2 overexpression protects against 6-hydroxydopamine-induced cell injury in the PC12 cell model of Parkinson's disease via regulation of the brahma-related gene 1/STAT3 pathway

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Abstract

According to published estimates, pyruvate kinase isoform M2 (PKM2) was expressed in low amounts in patients with Parkinson's disease (PD). However, the function and molecular mechanism of PKM2 in PD remain largely unknown. The main purpose of our study was to reveal the function and mechanism of PKM2 in the in vitro model of PD. Here, we show that PKM2 decreased in PC12 cells after 6-hydroxydopamine (6-OHDA) treatment, which inhibited PC12 cell survival and induced its apoptosis. PKM2 overexpression is required for 6-OHDA-induced PC12 cell survival. Moreover, up-regulated PKM2 expression suppressed PC12 cell apoptosis and caspase-3 activity compared with the 6-OHDA treatment alone group. Increased brahma-related gene 1 (Brg1) and p-STAT3 expression was observed in PKM2-overexpressed PC12 cells compared to those in 6-OHDA treated PC12 cells. Further studies suggested that Brg1 knockdown impeded the high expression of p-STAT3, which was induced by PKM2 overexpression. Finally, the STAT3 inhibitor reversed the effects of PKM2 on cell survival and apoptosis in 6-OHDA-induced PC12 cells. Our results suggest that PKM2 was involved in 6-OHDA-induced PC12 cell injury by mediating the Brg1/STAT3 pathway.

Graphical abstract: PKM2 overexpression protects against 6-hydroxydopamine-induced cell injury in the PC12 cell model of Parkinson's disease via regulation of the brahma-related gene 1/STAT3 pathway

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Publication details

The article was received on 08 Mar 2019, accepted on 29 Apr 2019 and first published on 14 May 2019


Article type: Paper
DOI: 10.1039/C9RA01760G
RSC Adv., 2019,9, 14834-14840
  • Open access: Creative Commons BY-NC license
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    PKM2 overexpression protects against 6-hydroxydopamine-induced cell injury in the PC12 cell model of Parkinson's disease via regulation of the brahma-related gene 1/STAT3 pathway

    L. Jiang, Y. Gao, G. Wang and J. Zhong, RSC Adv., 2019, 9, 14834
    DOI: 10.1039/C9RA01760G

    This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

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