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Myoglobin as a versatile peroxidase: Implications for a more important role for vertebrate striated muscle in antioxidant defense
- Mannino, Mark H., Patel, Rishi S., Eccardt, Amanda M., Perez Magnelli, Rodrigo A., Robinson, Chiron L.C., Janowiak, Blythe E., Warren, Daniel E., Fisher, Jonathan S.
- Comparative biochemistry and physiology 2019 v.234 pp. 9-17
- Carassius, NAD (coenzyme), NADP (coenzyme), acetaldehyde, acidosis, anaerobic conditions, antioxidant activity, caffeic acid, enzyme activity, ethanol, goldfish, horses, hydrogen peroxide, iron, muscles, myoglobin, oxidation, oxygen, pH, peroxidase, resveratrol, skeletal muscle, striated muscle
- Myoglobins (Mb) are ubiquitous proteins found in striated muscle of nearly all vertebrate taxa. Although their function is most commonly associated with facilitating oxygen storage and diffusion, Mb has also been implicated in cellular antioxidant defense. The oxidized (Fe3+) form of Mb (metMB) can react with hydrogen peroxide (H2O2) to produce ferrylMb. FerrylMb can be reduced back to metMb for another round of reaction with H2O2. In the present study, we have shown that horse skeletal muscle Mb displays peroxidase activity using 2,2′-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) and 3,3′,5,5′-tetramethylbenzidine (TMB) as reducing substrates, as well as the biologically-relevant substrates NADH/NADPH, ascorbate, caffeic acid, and resveratrol. We have also shown that ferrylMb can be reduced by both ethanol and acetaldehyde, which are known to accumulate in some vertebrate tissues under anaerobic conditions, such as anoxic goldfish and crucian carp, implying a potential mechanism for ethanol detoxification in striated muscle. We found that metMb peroxidase activity is pH-dependent, increasing as pH decreases from 7.4 to 6.1, which is biologically relevant to anaerobic vertebrate muscle when incurring intracellular lactic acidosis. Finally, we found that metMb reacts with hypochlorite in a heme-dependent fashion, indicating that Mb could play a role in hypochlorite detoxification. Taken together, these data suggest that Mb peroxidase activity might be an important antioxidant mechanism in vertebrate cardiac and skeletal muscle under a variety of physiological conditions, such as those that might occur in contracting skeletal muscle or during hypoxia.