EAE-induced upregulation of mitochondrial MnSOD is associated with increases of mitochondrial SGK1 and Tom20 protein in the mouse kidney cortex
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.
KeywordsNa,K-ATPase Reactive oxygen species Experimental autoimmune encephalomyelitis Ouabain Monensin HEK293 cells
Experimental autoimmune encephalomyelitis
Manganese superoxide dismutase
Reactive oxygen species
Translocase of the outer membrane subunit 20
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.
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