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Sialyltransferase7A, a Klf4-responsive gene, promotes cardiomyocyte apoptosis during myocardial infarction

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Abstract

Myocardial infarction (MI) is one major cause of heart failure through its induction of cardiomyocyte death. However, the molecular mechanisms associated with MI-induced cardiomyocyte apoptosis in the context of sialylation of heart are not yet understood. In this study, we found that sialyltransferase7A (Siat7A), one of the members of sialyltransferase family, was significantly increased in the ischemic myocardium, as well as in the human cardiomyocyte cell line AC16 under hypoxic condition. The Sialyl-Tn antigen (Neu5Acα2–6GalNAc-O-Ser/Thr) synthesized by Siat7A also increased in the AC16 cardiomyocytes following hypoxic stimulus. Increased Siat7A promoted cardiomyocyte apoptosis. The knockdown of Siat7A expression reduced cardiomyocyte apoptosis in both of vivo and vitro. Furthermore, the decreased extracellular signal-regulated kinase ERK1 and ERK2 (ERK1/2) activity was involved in the Siat7A-induced cardiomyocyte apoptosis. Notably, we showed that Krüppel-like factor 4 (Klf4), one of the transcription factors, specifically bound to the Siat7A promoter by ChIP assays. Deletion and mutagenesis analysis identified that Klf4 could transactivate the Siat7A promoter region (nt −655 to −636 bp). The upregulated Siat7A expression, which was paralleled by the increased Klf4 in the ischemic myocardium, contributed to cardiomyocyte apoptosis. Our study suggests Siat7A could be a valuable target for developing treatments for MI patients.

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Acknowledgments

This work is supported by National Natural Science Foundation of China Research Grant (No. 81200155 to Dongmei Zhang, No. 81402260 to Chuanchun Han, and No. 81372853 to Pixu Liu), Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT) to Pixu Liu, Liaoning Provincial Climbing Scholars Supporting Program of China to Pixu Liu, and Liaoning Provincial Natural Science Foundation of China (No. 2014023011) to Pixu Liu.

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The authors have nothing to disclose. On behalf of all authors, the corresponding author states that there is no conflict of interest.

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    1. Department of Physiology, Dalian Medical University, Dalian, People’s Republic of China

      Dongmei Zhang, Liang Zhu, Jingzhou Mu, Qiong Zhu & Zhenzhen Zhou

    2. Pathology Department of Dalian Medical University, Dalian, People’s Republic of China

      Chunmei Li

    3. Anatomy Department of Dalian Medical University, Dalian, People’s Republic of China

      Yuanshan Fu

    4. Institute of Cancer Stem Cell, Dalian Medical University, Dalian, People’s Republic of China

      Pixu Liu & Chuanchun Han

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    D. Zhang and L. Zhu contributed equally to this work.

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    Zhang, D., Zhu, L., Li, C. et al. Sialyltransferase7A, a Klf4-responsive gene, promotes cardiomyocyte apoptosis during myocardial infarction. Basic Res Cardiol 110, 28 (2015). https://doi.org/10.1007/s00395-015-0484-7

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