Journal
AGING-US
Volume 13, Issue 16, Pages 20569-20584Publisher
IMPACT JOURNALS LLC
Keywords
myocardial ischemia; reperfusion injury; NPAS2; CX3CL1; autophagy
Categories
Funding
- Top-level Clinical Discipline Project of Shanghai Pudong District [PWYgf2018-02]
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The study showed that overexpression of NPAS2 interacts with Cry2 to promote the transcriptional activity of CX3CL1, improving rat myocardial ischemia-reperfusion injury and cardiomyocyte apoptosis. Additionally, NPAS2 regulates the downstream AKT/mTOR pathway to inhibit autophagy and alleviate cardiac I/R injury.
Background: Myocardial ischemia/reperfusion (I/R) injury is common during the treatment of cardiovascular diseases. Neuronal PAS Domain Protein 2 (NPAS2) is one of the core genes that control the rhythm of the biological clock. NPAS2 also regulates the biological rhythm. Results: The rat I/R model showed that the expression of NPAS2 decreased with the increase of reperfusion time. Overexpressing NPAS2 adenovirus (ad-NPAS2) was injected into IR rat which demonstrated that adNPAS2 ameliorated rats I/R injury. A hypoxia/reoxygenation (H/R) model in rat cardiomyocytes showed that ad-NPAS2 inhibited cardiomyocyte apoptosis. Co-Immunoprecipitation results showed that there is an interaction between NPAS2 and Cry2. Knockdown of Cry2 aggravated the cardiomyocyte apoptosis induced by H/R. Additionally, NPAS2 directly act on the promoter region of CX3CL1. Knockdown of CX3CL1 reverse the protective effect of ad-NPAS2 on rat myocardial ischemia-reperfusion injury and H/R-induced cardiomyocyte apoptosis. CX3CL1 also regulates autophagy through the downstream AKT/mTOR pathway. Conclusions: research demonstrated that overexpression of NPAS2 interacts with Cry2 and promotes the transcriptional activity of CX3CL1. Moreover, overexpression of NPAS2 regulates the downstream AKT/mTOR pathway to inhibit autophagy in order to improve rat cardiac I/R injury.
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