Role of myoglobin in the antioxidant defense of the heart.


Although the primary function of myoglobin (Mb) has been considered to be cellular O2 storage and supply, recent studies have shown that Mb in addition can act as NO oxidase. Here we report that Mb also significantly contributes to the attenuation of oxidative stress in cardiac muscle. In support of this hypothesis, we found that in isolated perfused hearts of Mb-deficient (myo-/-) mice oxidative challenge by intracoronary infused H2O2 (1-300 microM) or superoxide formed by 2,3-dimethoxy-1,4-naphtoquinone (0.1-30 microM), respectively, depressed cardiac contractility to a greater extent than in wild-type (WT) hearts, e.g., up to [H2O2] = 10 microM there was a significant left ventricular developed pressure (LVDP) decrease in myo-/- hearts only (90.4+/-4.2 vs. 98.1+/-0.7% of control, n=6, P<0.05). Likewise in an ischemia/reperfusion protocol, myo-/- hearts showed a delayed recovery of postischemic function as compared with WT controls (e.g., LVDP was 35.6+/-7.5 vs. 22.4+/-5.3 mmHg, respectively, after 10 min of reperfusion, P<0.05, n=8), which correlated well with an enhanced release of reactive oxygen species in myo-/- hearts as measured by online lucigenin-enhanced chemiluminescence [e.g. 465+/-87 relative light units (RLU) in myo-/- vs. 287+/-73 RLU in WT after 2.5 min of reperfusion, P<0.05, n=8]. (31)P NMR spectroscopy revealed concomitantly a more pronounced phosphocreatine overshoot during reperfusion in the knockout but only minute alterations in ATP and pHi. Our data show that lack of Mb leads to increased vulnerability of cardiac function to oxidative challenge either pharmacologically induced or endogenously generated. We propose that Mb is a key element influencing redox pathways in cardiac muscle to functionally and metabolically protect the heart from oxidative damage.

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@article{Floegel2004RoleOM, title={Role of myoglobin in the antioxidant defense of the heart.}, author={Ulrich Floegel and Axel Goedecke and Lars-Oliver Klotz and Juergen Schrader}, journal={FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, year={2004}, volume={18 10}, pages={1156-8} }