title: SOX6 and PDCD4 enhance cardiomyocyte apoptosis through LPS-induced miR-499 inhibition.
abstract: Sepsis-induced cardiac apoptosis is one of the major pathogenic factors in myocardial dysfunction. As it enhances numerous proinflammatory factors, lipopolysaccharide (LPS) is considered the principal mediator in this pathological process. However, the detailed mechanisms involved are unclear. In this study, we attempted to explore the mechanisms involved in LPS-induced cardiomyocyte apoptosis. We found that LPS stimulation inhibited microRNA (miR)-499 expression and thereby upregulated the expression of SOX6 and PDCD4 in neonatal rat cardiomyocytes. We demonstrate that SOX6 and PDCD4 are target genes of miR-499, and they enhance LPS-induced cardiomyocyte apoptosis by activating the BCL-2 family pathway. The apoptosis process enhanced by overexpression of SOX6 or PDCD4, was rescued by the cardiac-abundant miR-499. Overexpression of miR-499 protected the cardiomyocytes against LPS-induced apoptosis. In brief, our results demonstrate the existence of a miR-499-SOX6/PDCD4-BCL-2 family pathway in cardiomyocytes in response to LPS stimulation.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing, China.
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Beijing Jianhua Experimental School, Yuquan Road 66, Haidian District, Beijing, China.
authors.forename: Jiaji
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Road NE, Atlanta, GA, 30322, USA.
authors.forename: Siyu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing, China.
authors.forename: Yuyao
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing, China.
authors.forename: Kangtao
authors.initials: K
authors.lastname: Ma
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing, China. chunyanzhou@bjmu.edu.cn.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D002478:Cells, Cultured; D006367:HeLa Cells; D006352:Heart Ventricles / Q000166:cytology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000502:physiology*; D034622:RNA Interference / Q000276:immunology; D017207:Rats, Sprague-Dawley; D055755:SOXD Transcription Factors / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D008070:Lipopolysaccharides; C558425:MIRN499 microRNA, rat; D035683:MicroRNAs; C467042:Pdcd4 protein, rat; D055755:SOXD Transcription Factors
keywords: Apoptosis; Cardiomyocyte; LPS; PDCD4; SOX6; miR-499