The role of glutaredoxin-2 in regulating superoxide/hydrogen peroxide formation from liver and cardiac tissue

Chalker, Julia (2017) The role of glutaredoxin-2 in regulating superoxide/hydrogen peroxide formation from liver and cardiac tissue. Masters thesis, Memorial University of Newfoundland.

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Abstract

S-glutathionylation has been found to control the production of mitochondrial reactive oxygen species (ROS), regulated by glutaredoxin-2 (GRX2). GRX2 deficiency is associated with heart disease, neurological deficits, and cataracts, which have all been linked to increased ROS production. Using GRX2⁺/⁻ and GRX2⁻/⁻ mice, we have shown that GRX2 controls the emission of superoxide (O2●⁻) /hydrogen peroxide (H2O2) from liver and cardiac mitochondria in a tissue and substrate dependant manner. In cardiac tissue, GRX2⁺/⁻ and GRX2⁻/⁻ mitochondria display increased O2●⁻/H2O2 production compared to WT when metabolizing succinate. In liver tissue, mitochondria isolated from GRX2⁻/⁻ mice show a significant decrease in O2●⁻/H2O2 emission when metabolizing pyruvate and 2-oxoglutarate. Our results show that GRX2 plays an important role in controlling mitochondrial ROS production in different tissues. Future work into the method of ROS control by GRX2 could highlight a method to control ROS production and prevent tissue damage from increased ROS.

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