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Research Articles

NURR1 inhibition reduces hypoxia-mediated cardiomyocyte necrosis via blocking Mst1-JNK-mPTP pathway

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Pages 350-358 | Received 11 Aug 2019, Accepted 27 Oct 2019, Published online: 22 Nov 2019
 

Abstract

Context: Although many studies have investigated the molecular mechanisms underlying hypoxia-related cardiomyocyte damage, the role of necrosis in cardiomyocyte death.

Objective: The aim of our study is to explore the pathological role of nuclear receptor related 1 protein (NURR1) in regulating cardiomyocyte viability under hypoxia stress.

Materials and methods: Cardiomyocyte was treated with hypoxia and siRNA against NURR1 was transfected into cardiomyocyte. Pathway agonist was used to activate the Mst1-JNK-mPTP pathway in cardiomyocyte.

Results: In our study, the expression of NURR1 was rapidly increased in cardiomyocyte transfected with NURR1. Knockout of NURR1 could promote cardiomyocyte survival, reduce cell death and repress inflammation response. Mechanistically, NURR1 upregulation was associated with an activation of Mst1-JNK pathway and the latter promoted the mPTP opening in cardiomyocyte. Excessive mPTP opening was followed by cardiomyocyte necrosis and this effect could be reversed by NURR1 deletion. Besides, re-activation of Mst1-JNK pathway could abolish the protective effects of NURR1 deletion on cardiomyocytes, as evidenced by increased cell survival and decreased necrosis. Besides, re-activation of Mst1-JNK pathway also abolished NURR1 deletion-mediated mPTP opening.

Conclusions: Hypoxia-mediated cardiomyocyte death is associated with NURR1 upregulation which contributes to the activation Mst1-JNK-mPTP pathways.

Disclosure statement

The authors declare that they have no conflicts of interest.

Authors' contributions

GQM made substantial contributions to the concept and design of the present study, YWL and GQM contributed to the performance of experiments, data analysis and interpretation, and manuscript writing.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

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