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

Abstract

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 O2 equilibria, carbon monoxide (CO) and O2 binding kinetics, thiol S-nitrosation, nitrite reductase activities, and peroxidase activities. Mb1 has O2 affinity and nitrite reductase activity comparable to most vertebrate muscle Mbs, consistent with established roles for Mbs in O2 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 O2 and CO kinetics, a lower O2 affinity, and is slower at converting nitrite into NO. Mb2 is therefore unlikely to be primarily involved in either O2 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.