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Minocycline promotes cardiomyocyte mitochondrial autophagy and cardiomyocyte autophagy to prevent sepsis-induced cardiac dysfunction by Akt/mTOR signaling

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Abstract

Myocardial damage is responsible for the high mortality of sepsis. However, the underlying mechanism is not well understood. Cardiomyocyte autophagy alleviates the cardiac injury caused by myocardial infarction. Enhanced cardiomyocyte autophagy also has protective effects against cardiomyocyte mitochondrial injury. Minocycline enhances autophagy in many types of cells under different types of pathological stress and can be easily taken up by cardiomyocytes. The present study investigated whether minocycline prevented myocardial injury caused by sepsis and whether cardiomyocyte autophagy participated in this process. The results indicated that minocycline enhanced cardiomyocyte mitochondrial autophagy and cardiomyocyte autophagy and improved myocardial mitochondrial and cardiac function. Minocycline upregulated protein kinase B (Akt) phosphorylation, inhibited mTORC1 expression and enhanced mTORC2 expression. In conclusion, minocycline enhanced cardiomyocyte mitochondrial autophagy and cardiomyocyte autophagy and improved cardiac function. The underlying mechanisms were associated with mTORC1 inhibition and mTORC2 activation. Thus, our findings suggest that minocycline may represent a potential approach for treating myocardial injury and provide novel insights into the underlying mechanisms of myocardial injury and dysfunction after sepsis.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 81670204); National Natural Science Foundation of China (Grant No. 81171839); Funding of Xiamen University (Grant No. 20720170106).

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Dongdong Sun, Lichao Hou, Erfei Zhang, and Xiaoying Zhao designed the experiments, analyzed and interpreted the data and drafted the manuscript. Li Zhang, Nan Li, Jingqi Yan, Ke Tu, Ruhu Yan, Jianqiang Hu and Mingming Zhang, were involved in the data acquisition. All authors revised the manuscript critically and approved the final version to be published. Dongdong Sun and Lichao Hou are responsible for the integrity of the work as a whole.

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Correspondence to Dongdong Sun or Lichao Hou.

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Zhang, E., Zhao, X., Zhang, L. et al. Minocycline promotes cardiomyocyte mitochondrial autophagy and cardiomyocyte autophagy to prevent sepsis-induced cardiac dysfunction by Akt/mTOR signaling. Apoptosis 24, 369–381 (2019). https://doi.org/10.1007/s10495-019-01521-3

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