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Chang W, Feng M, Li Y, et al. MKP1 overexpression reduces TNF-α-induced cardiac injury via suppressing mitochondrial fragmentation and inhibiting the JNK-MIEF1 pathways. J Cell Physiol. 2019;doi: 10.1002/jcp.28273.
Chang, W., Feng, M., Li, Y., Sun, Y., & Sun, L. (2019). MKP1 overexpression reduces TNF-α-induced cardiac injury via suppressing mitochondrial fragmentation and inhibiting the JNK-MIEF1 pathways. Journal of cellular physiology, . https://doi.org/10.1002/jcp.28273
Chang, Wei, et al. "MKP1 overexpression reduces TNF-α-induced cardiac injury via suppressing mitochondrial fragmentation and inhibiting the JNK-MIEF1 pathways." Journal of cellular physiology vol. (2019). doi: https://doi.org/10.1002/jcp.28273
Chang W, Feng M, Li Y, Sun Y, Sun L. MKP1 overexpression reduces TNF-α-induced cardiac injury via suppressing mitochondrial fragmentation and inhibiting the JNK-MIEF1 pathways. J Cell Physiol. 2019 Feb 10; doi: 10.1002/jcp.28273. Epub 2019 Feb 10. PMID: 30740674.
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J Cell Physiol. 2019 Feb 10; doi: 10.1002/jcp.28273. Epub 2019 Feb 10.

MKP1 overexpression reduces TNF-α-induced cardiac injury via suppressing mitochondrial fragmentation and inhibiting the JNK-MIEF1 pathways.

Journal of cellular physiology

Wei Chang, Min Feng, Yuexia Li, Ya Sun, Lulu Sun

Affiliations

  1. Department of Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  2. Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  3. Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

PMID: 30740674 DOI: 10.1002/jcp.28273

Abstract

Mitochondrial stress has been acknowledged as the pathogenesis for tumor necrosis factor-α (TNF-α)-induced septic cardiomyopathy. Recently, MAP kinase phosphatase 1 (MKP1) downregulation and mitochondrial fragmentation modulate the mitochondrial stress via multiple molecular mechanisms. Thereby, the goal of our current work is to figure out the functional role of mitochondrial fragmentation in TNF-α-induced septic cardiomyopathy. Our results exhibited that MKP1 expression was significantly repressed in hearts treated by TNF-α. Overexpression of MKP1 sustained cardiac function and attenuated cardiomyocytes death in TNF-α-treated hearts. At the molecular levels, decreased MKP1 induced mitochondrial stress, as indicated by mitochondrial calcium overloading, mitochondrial oxidative stress, mitochondrial antioxidant downregulation, mitochondrial membrane potential reduction, mitochondrial bioenergetics suppression, mitochondrial proapoptotic factors liberation, and caspase-9 apoptotic pathway activation. To the end, we illustrated that MKP1-modulated mitochondrial stress via mitochondrial fragmentation; reactivation of mitochondrial fragmentation abolished the protective effect of MKP1 overexpression on mitochondrial function. Further, MKP1 affected mitochondrial division in a mechanism through the JNK-MIEF1 axis. Blockade of JNK pathway abolished the regulatory actions of MKP1 on mitochondrial division. Altogether, our results identify MKP1 as a novel cardioprotective factor in TNF-α-related septic cardiomyopathy via affecting mitochondrial division by the way of JNK-MIEF1 signaling pathway. Therefore, MKP1 expression, mitochondrial fragmentation modification, and JNK-MIEF1 pathway modulation may be considered as potential therapeutic targets for the treatment of cardiac injury induced by sepsis.

© 2019 Wiley Periodicals, Inc.

Keywords: JNK-MIEF1 pathway; MKP1; TNF-α; mitochondrial fragmentation; septic cardiomyopathy

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