| Autor: |
Balamurugan Packialakshmi, Xiaoming Zhou |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
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| Zdroj: |
PLoS ONE, Vol 13, Iss 4, p e0196277 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0196277 |
| Popis: |
Increases of the activity of mitochondrial electron transport chain generally lead to increases of production of ATP and reactive oxygen species (ROS) as by-products. MnSOD is the first line of defense against the stress induced by mitochondrial ROS. Our previous studies demonstrated that EAE progression increased Na,K-ATPase activity in the mouse kidney cortex. Since mitochondria are the major source of ATP, our present studies were sought to determine whether EAE progression increased mitochondrial activity. We found that severe EAE increased mitochondrial complex II and IV activities without significantly affecting complex I activity with corresponding increases of ROS in the isolated mitochondria and native kidney cortex. Severe EAE augmented both cytosolic and mitochondrial MnSOD protein levels and activities and decreased the specific activity of mitochondrial MnSOD when the total mitochondrial MnSOD activity was normalized to the protein level. Using HEK293 cells as a model free of interference from immune reactions, we found that activation of Na,K-ATPase by monensin for 24 hours increased complex II activity, mitochondrial ROS and MnSOD protein abundance, and decreased the specific activity of the mitochondrial MnSOD. Inhibition of Na,K-ATPase by ouabain or catalase attenuated the effects of monensin on the mitochondrial complex II activity, ROS, MnSOD protein level and specific activity. Kockdown of MnSOD by RNAi reduced the mitochondrial ability to generate ATP. In conclusion, EAE increases mitochondrial activity possibly to meet the energy demand from increased Na,K-ATPase activity. EAE increases mitochondrial MnSOD protein abundance to compensate for the loss of the specific activity of the enzyme, thus minimizing the harmful effects of ROS. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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