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Published on: February 24, 2018
Mitochondrial reactive oxygen species: which ROS signals cardioprotection?
Anders O Garlid1, Martin Jaburek, Jeremy P Jacobs
1Department of Biology, Portland State University, Portland, Oregon; and.
The study identifies the signaling reactive oxygen species (ROS) involved in heart protection. Results suggest a downstream product of hydroxyl radical (HO·), likely from phospholipid oxidation, carries the ROS signal, not hydrogen peroxide (H2O2).
Area of Science:
- Cardiovascular Physiology
- Mitochondrial Biology
- Biochemistry
Background:
- Mitochondria protect the heart via ATP-sensitive potassium channels (mitoKATP).
- mitoKATP opening involves reactive oxygen species (ROS) and PKCε activation.
- The specific signaling ROS in this process remains unidentified.
Purpose of the Study:
- To identify the endogenous signaling ROS responsible for mitoKATP channel opening and cardioprotection.
- To investigate the roles of superoxide (O2(·-)), hydrogen peroxide (H2O2), and hydroxyl radical (HO(·)) in this signaling pathway.
Main Methods:
- Utilized isolated respiring rat heart mitochondria preincubated with ATP and diazoxide.
- Tested agents that scavenge ROS or block ROS transformations to assess interference with mitoKATP persistent opening.
- Assayed mitochondria for the formation of the persistent phosphorylated open state.
Main Results:
- Dimethylsulfoxide (DMSO), dimethylformamide (DMF), deferoxamine, Trolox, and bromoenol lactone interfered with the ROS-dependent open state.
- Catalase did not interfere, excluding hydrogen peroxide (H2O2) as the signaling ROS.
- DMF inhibited both ischemic preconditioning and diazoxide-induced cardioprotection.
Conclusions:
- The signaling ROS is not H2O2.
- The ROS signal is likely a downstream product of hydroxyl radical (HO(·)).
- Phospholipid oxidation products are implicated as the likely signaling molecules.
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