SOX6 and PDCD4 enhance cardiomyocyte apoptosis through LPS-induced miR-499 inhibition.

Zhuqing Jia,Weiping Wang,Kangtao Ma,Siyu Liu,Chunyan Zhou,Qiong Shi,Yuyao Tian,Qin Lu,Ping Chen,Jiaji Wang

doi:10.1007/s10495-015-1201-6

Zhuqing Jia, Weiping Wang + Show 8 more

Open Access

https://doi.org/10.1007/s10495-015-1201-6

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Journal: Apoptosis	Publication Date: Dec 10, 2015
Citations: 101	License type: CC BY 4.0

Affiliation: Peking University, Emory University

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s10495-015-1201-6) contains supplementary material, which is available to authorized users.

Highlights

Present AddressDepartment of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Road NE, Atlanta, GA 30322, USA the cardiomyocytes against LPS-induced apoptosis. In brief, our results demonstrate the existence of a miR-499SOX6/PDCD4-BCL-2 family pathway in cardiomyocytes in response to LPS stimulation
Sepsis-induced myocardial functional disorder is one of the main predictors of morbidity and mortality of sepsis [1]; apoptosis is one of the major contributors to the pathophysiology of sepsis [2]
We attempted to explore the mechanisms involved in LPS-induced cardiomyocyte apoptosis

Summary

Present Address

Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Road NE, Atlanta, GA 30322, USA the cardiomyocytes against LPS-induced apoptosis. In brief, our results demonstrate the existence of a miR-499SOX6/PDCD4-BCL-2 family pathway in cardiomyocytes in response to LPS stimulation.

Introduction

Results

F: CTGACGCCCTTCACCGCGAG 235

Discussion

Compliance with ethical standards