MicroRNA-155-5p/EPAS1/interleukin 6 pathway participated in the protection function of sphingosylphosphorylcholine to ischemic cardiomyocytes.

Yao, Yujuan; Zhou, Jinrun; Lu, Chenchen; Sun, Wenjing; Kong, Weihua; Zhao, Jing

Yao, Yujuan; Zhou, Jinrun; Lu, Chenchen; Sun, Wenjing; Kong, Weihua; Zhao, Jing.

Afiliación

Yao Y; Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao 266237, PR China.
Zhou J; Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao 266237, PR China.
Lu C; Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao 266237, PR China.
Sun W; Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao 266237, PR China.
Kong W; Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao 266237, PR China.
Zhao J; Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao 266237, PR China. Electronic address: jingzhao@sdu.edu.cn.

Life Sci ; 264: 118692, 2021 Jan 01.

Article en En | MEDLINE | ID: mdl-33130081

RESUMEN

AIM: Previous research in our laboratory found that a biologically active sphingomyelin metabolite, sphingosylphosphorylcholine (SPC), can inhibit myocardial cell apoptosis caused by ischemia with an unknown mechanism. Here, we aimed to study the possible participation of EPAS1 in the protection process of SPC. METHODS: The rat cardiomyocytes deprived of serum were used to mimic ischemic-caused apoptosis, then treated with or without SPC. The expression and nuclear shift of EPAS1 were detected by western blot and immunofluorescence, and its function was studied using its siRNA. KEY FINDING: Our research shows that SPC inhibited serum starvation caused cardiomyocyte apoptosis, accompanied by the up-regulation and nucleus translocation of EPAS1. EPAS1 levels did not change when its transcript was blocked by Actinomycin D, which prompted us to search for a post-transcription mechanism for its increased expression, and finally found that miR-155-5p, regulated by STAT3, was a new post-transcription regulator to EPAS1. Further investigation found that EPAS1 participated in the protective effect of SPC is mainly achieved by activating the downstream target gene, interleukin-6 (IL-6). SIGNIFICANCE: Our results expand our understanding of the biological functions of SPC, and bring a new pathway as a potential therapeutic target to the treatment of cardiovascular diseases caused by myocardial apoptosis.

Asunto(s)

Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo; Cardiotónicos/farmacología; Interleucina-6/metabolismo; MicroARNs/metabolismo; Isquemia Miocárdica/genética; Isquemia Miocárdica/patología; Miocitos Cardíacos/patología; Fosforilcolina/análogos & derivados; Esfingosina/análogos & derivados; Animales; Apoptosis/efectos de los fármacos; Apoptosis/genética; Secuencia de Bases; Hipoxia de la Célula/efectos de los fármacos; Núcleo Celular/efectos de los fármacos; Núcleo Celular/metabolismo; Regulación hacia Abajo/efectos de los fármacos; Factor 2 de Crecimiento de Fibroblastos/metabolismo; Células HEK293; Humanos; MicroARNs/genética; Modelos Biológicos; Miocitos Cardíacos/efectos de los fármacos; Miocitos Cardíacos/metabolismo; Fosforilación/efectos de los fármacos; Fosforilcolina/farmacología; ARN Mensajero/genética; ARN Mensajero/metabolismo; Ratas Wistar; Factor de Transcripción STAT3/metabolismo; Transducción de Señal/efectos de los fármacos; Esfingosina/farmacología; Transcripción Genética/efectos de los fármacos; Factor A de Crecimiento Endotelial Vascular/metabolismo

Palabras clave

Apoptosis; Cardiomyocytes; EPAS1; MiR-155-5p; SPC

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosforilcolina / Esfingosina / Cardiotónicos / Interleucina-6 / Isquemia Miocárdica / Miocitos Cardíacos / MicroARNs / Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Life Sci Año: 2021 Tipo del documento: Article Pais de publicación: Países Bajos

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