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Stress-inflammatory/oxidative pathway activation results in increased transforming growth factor- (TGF-) signaling, which activates SMAD3 and increased NADPH Oxidase 2(NOX2) expression and activity at the RyR2 channel, leading to oxidation and calstabin 2 depletion from the channel macromolecular complex

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Extraction buffer containing 80% methanol with 500 nM metabolomics amino acid standard mix (Cambridge Isotopes Laboratory) was added to each to reach a final concentration of 10 mg ml 1