Journal
ANTIOXIDANTS & REDOX SIGNALING
Volume 31, Issue 9, Pages 664-670Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2018.7697
Keywords
H2O2 gradients; chemogenetics; thioredoxin reductase; HyPer; D-amino acid oxidase
Funding
- Russian Science Foundation [17-14-01086]
- DFG [IRTG 1816]
- NIH [P30 DK057521]
- Brigham and Women's Hospital Health and Technology Innovation Award
- Swedish Cancer Society
- Swedish Research Council
- Knut and Alice Wallenberg Foundations
- Russian Ministry of Education and Science [RFMEFI62117X0018]
- Russian Science Foundation [17-14-01086] Funding Source: Russian Science Foundation
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Cellular antioxidant systems control the levels of hydrogen peroxide (H2O2) within cells. Multiple theoretical models exist that predict the diffusion properties of H2O2 depending on the rate of H2O2 generation and amount and reaction rates of antioxidant machinery components. Despite these theoretical predictions, it has remained unknown how antioxidant systems shape intracellular H2O2 gradients. The relative role of thioredoxin (Trx) and glutathione systems in H2O2 pattern formation and maintenance is another disputed question. Here, we visualized cellular antioxidant activity and H2O2 gradients formation by exploiting chemogenetic approaches to generate compartmentalized intracellular H2O2 and using the H2O2 biosensor HyPer to analyze the resulting H2O2 distribution in specific subcellular compartments. Using human HeLa cells as a model system, we propose that the Trx system, but not the glutathione system, regulates intracellular H2O2 gradients. Antioxid. Redox Signal. 00, 000-000.
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