CK1α protects cardiomyocytes in sepsis-induced myocardial depression by repressing the interaction of ATG5 with myD88/NF-kappaB signaling

Author:

Sun Hongpeng,Wu Yanmei

Abstract

Purpose: To explore the effects of casein kinase 1α (CK1α) on cardiomyocytes in sepsis-induced myocardial depression.Methods: Colorectal ligation puncture (CLP) surgery was performed for the establishment of the mouse model. Total RNAs of the lungs, kidneys, liver tissues and alveolar macrophages were extracted using TRIzol™ reagent, while gene expression analysis was performed by quantitative polymerase chain reaction (qPCR) following reverse transcription. Western blot was employed to evaluate protein expression, and echocardiography was conducted to assess cardiac function. Immunofluorescent assay was performed to determine the expression of p-FOXO3a in primary cardiomyocytes.Results: Inhibition of CK1α impaired autophagy influx, and significantly increased inflammatory cytokines in H9C2 cells after lipopolysaccharide (LPS) treatment (p < 0.05). Moreover, aberrant activation of the Toll-like receptor 4(TLR4)/myD88/NF-kappaB pathway was observed in the H9C2 cell line after LPS treatment (p < 0.05). Immunoprecipitation analysis revealed an interaction between MyD88 and autophagy-related gene 5 (Atg5), and cardiac dysfunction in mice intravenously injectedwith an adenoviral vector containing shRNA (casein kinase 1 α) CSNK1A1 was suppressed (p < 0.05). In contrast, overexpression of CK1α remarkably improved cardiac systolic function (p < 0.05), the expression of inflammatory cytokines was repressed, and autophagy was enhanced in the hearts of mice with the specific overexpression of CSNK1A1 in cardiomyocytes (p < 0.05). In Atg5-deficient mice pretreated with DC661, the protective effect of adenoviral vector containing CK1α overexpression was eliminated.Conclusion: CK1α protects cardiomyocytes during sepsis after the inhibition of TLR/MyD88/NF-kappaBpathway via interaction of Atg5 with MyD88. The results of the current study may provide new insights into the treatment of sepsis-induced myocardial depression.

Publisher

African Journals Online (AJOL)

Subject

Pharmacology (medical),Pharmaceutical Science

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