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Supplementary Material for: Moderate Hydrogen Peroxide Postconditioning Ameliorates Ischemia/Reperfusion Injury in Cardiomyocytes via STAT3-Induced Calcium, ROS, and ATP Homeostasis

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posted on 10.12.2020, 10:17 by Wu L., Huang W., Yu C., Li Y.
Introduction: Moderate hydrogen peroxide postconditioning (H2O2PoC) activates signal transducer and activator of transcription 3 (STAT3) to alleviate mitochondrial calcium overload during cardiac ischemia/reperfusion (I/R). However, the initial time window of STAT3-induced calcium hemostasis, the production of reactive oxygen species (ROS) and adenosine triphosphate (ATP) in H2O2PoC, and its regulated mechanism remain unknown. This study aimed to investigate H2O2PoC-induced homeostasis of calcium, ROS and ATP, and the role of STAT3 in the regulation. Methods: Isolated rat cardiomyocytes were exposed to H2O2PoC and Janus kinase 2 (JAK2)/STAT3 inhibitor AG490 during I/R. Ca2+ transients, cell contraction, intracellular calcium concentration, ROS production, ATP contents, phosphorylation of STAT3, gene and protein expression of manganese superoxide dismutase (MnSOD), metallothionein 1 (MT1) and metallothionein 2 (MT2), as well as activities of mitochondrial complex I and complex II were detected. Results: Moderate H2O2PoC improved post-ischemic Ca2+ transients and cell contraction recovery as well as alleviated cytosolic and mitochondrial calcium overload, which were abrogated by AG490 in rat cardiomyocytes. Moderate H2O2PoC increased ROS production and rate of ROS production at early reperfusion in rat I/R cardiomyocytes, and this phenomenon was also abrogated by AG490. Notably, the expression of phosphorylated nuclear STAT3; gene and protein expression of MnSOD, MT1, and MT2; and activities of mitochondrial complex I and complex II were upregulated by moderate H2O2PoC but downregulated by AG490. Conclusion: These findings indicated that the cardioprotection of moderate H2O2PoC against cardiac I/R could be associated with activated STAT3 at early reperfusion to maintain calcium, ROS, and ATP homeostasis in rat cardiomyocytes.

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