Functional differentiation of myoglobin isoforms in hypoxia-tolerant carp indicates tissue-specific protective roles

Helbo S, Dewilde S, Williams DR, Berghmans H, Berenbrink M, Cossins AR, Fago A. Functional differentiation of myoglobin isoforms in hypoxia-tolerant carp indicates tissue-specific protective roles. Am J Physiol Regul Integr Comp Physiol 302: R693-R701, 2012. First published December 14, 2011; doi:10.1152/ajpregu.00501.2011.-Because of a recent whole genome duplication, the hypoxia-tolerant common carp and goldfish are the only vertebrates known to possess two myoglobin (Mb) paralogs. One of these, Mb1, occurs in oxidative muscle but also in several other tissues, including capillary endothelial cells, whereas the other, Mb2, is a unique isoform specific to brain neurons. To help understand the functional roles of these diverged isoforms in the tolerance to severe hypoxia in the carp, we have compared their O-2 equilibria, carbon monoxide (CO) and O-2 binding kinetics, thiol S-nitrosation, nitrite reductase activities, and peroxidase activities. Mb1 has O-2 affinity and nitrite reductase activity comparable to most vertebrate muscle Mbs, consistent with established roles for Mbs in O-2 storage/delivery and in maintaining nitric oxide (NO) homeostasis during hypoxia. Both Mb1 and Mb2 can be S-nitrosated to similar extent, but without oxygenation-linked allosteric control. When compared with Mb1, Mb2 displays faster O-2 and CO kinetics, a lower O-2 affinity, and is slower at converting nitrite into NO. Mb2 is therefore unlikely to be primarily involved in either O-2 supply to mitochondria or the generation of NO from nitrite during hypoxia. However, Mb2 proved to be significantly faster at eliminating H2O2, a major in vivo reactive oxygen species (ROS), suggesting that this diverged Mb isoform may have a specific protective role against H2O2 in the carp brain. This property might be of particular significance during reoxygenation following extended periods of hypoxia, when production of H2O2 and other ROS is highest.