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EAE-induced upregulation of mitochondrial MnSOD is associated with increases of mitochondrial SGK1 and Tom20 protein in the mouse kidney cortex

  • Sharanpreet Hira
  • Balamuguran Packialakshmi
  • Xiaoming ZhouEmail author
Original Paper

Abstract

Our previous demonstration that severe experimental autoimmune encephalomyelitis (EAE) increases MnSOD protein abundance in the mouse kidney cortex led this study to elucidate the underlying mechanism with monensin-treated HEK293 cells as a model. Severe EAE increases mitochondrial protein abundance of SGK1 kinase and Tom20, a critical subunit of mitochondrial translocase in the renal cortex. In HEK293 cells, catalase inhibits monensin-induced increases of mitochondrial SGK1 and Tom20 protein levels. Further, GSK650394, a specific inhibitor of SGK1 reduces monensin-induced increase of mitochondrial protein abundance of Tom20 and MnSOD. Finally, RNAi of Tom20 reduces the effect of monensin on MnSOD. MnSOD and Tom20 physically associate with each other. In conclusion, in HEK293 cells, mitochondrial reactive oxygen species increase protein abundance of mitochondrial SGK1, which leads to a rise of mitochondrial Tom20, resulting in importing MnSOD protein into the mitochondria. This could be a mechanism by which severe EAE up-regulates mitochondrial MnSOD in the kidney cortex.

Keywords

Na,K-ATPase Reactive oxygen species Experimental autoimmune encephalomyelitis Ouabain Monensin HEK293 cells 

Abbreviations

EAE

Experimental autoimmune encephalomyelitis

MnSOD

Manganese superoxide dismutase

ROS

Reactive oxygen species

Tom20

Translocase of the outer membrane subunit 20

Notes

Acknowledgements

This work was funded in part by the grant (MED-83-3923) from the collaborative health initiative research program between the National Heart Lung and Blood Institute and the Henry Jackson Foundation for the Advancement of Military Medicine, the National Multiple Sclerosis Society Grant PP3448 and a Uniformed Services University education grant. The authors thank Dr. Louis Pangaro for his help in obtaining the education grant.

Disclaimer

The content and views expressed in this article are the sole responsibility of the authors and do not necessarily reflect the views or policies of the Department of Defense or US Government. Mention of trade names, commercial products, or organizations does not imply endorsement by the Department of Defense or US Government.

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Copyright information

© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2019

Authors and Affiliations

  1. 1.Department of MedicineUniformed Services University of the Health SciencesBethesdaUSA

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