Oxygen, oxidative stress, hypoxia, and heart failure
J. Clin. Invest. Frank J. Giordano, et al. 115:500 doi:10.1172/JCI24408 [
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Figure 2Mechanisms by which ROS can alter the structure and function of cardiac muscle. ATII binds a G-protein_associated receptor, initiating a cascade of events that involves activation of O
2–– production by the NAD(P)H oxidase NOX2. O
2–– is converted by SOD into H
2O
2 and
–OH that mediates activation of MAPKs via a tyrosine kinase. MAPK activation can lead to cardiac hypertrophy or to apoptosis. The ROS that is generated can also signal through ASK-1 to induce cardiac hypertrophy, apoptosis, or phosphorylate troponin T, an event that reduces myofilament sensitivity and cardiac contractility. NO production by the NO synthases iNOS and eNOS can interact with O
2–– to form ONOO
––. ONOO
–– can cause lipid peroxidation, an event that can alter ion channel and ion pump function. Catalase and glutathione reductase (GPx) are shown as enzymatic pathways to produce water and oxygen from H
2O
2.
