Hypoxia-inducible myoglobin expression in nonmuscle tissues

Abstract

Myoglobin (Myg) is an oxygen-binding hemoprotein that is widely thought to be expressed exclusively in oxidative skeletal and cardiac myocytes, where it plays a key role in coping with chronic hypoxia. We now show in a hypoxia-tolerant fish model, that Myg is also expressed in a range of other tissues, including liver, gill, and brain. Moreover, expression of Myg transcript was substantially enhanced during chronic hypoxia, the fold-change induction being far greater in liver than muscle. By using 2D gel electrophoresis, we have confirmed that liver expresses a protein corresponding to the Myg-1 transcript and that it is significantly up-regulated during hypoxia. We have also discovered a second, unique Myg isoform, distinct from neuroglobin, which is expressed exclusively in the neural tissue but whose transcript expression was unaffected by environmental hypoxia. Both observations of nonmuscle expression and a brain-specific isoform are unprecedented, indicating that Myg may play a much wider role than previously understood and that Myg might function in the protection of tissues from deep hypoxia and ischemia as well as in reoxygenation and reperfusion injury.

A globin in every cell?

“…In human skeletal muscle, Mb in mitochondriarich oxidative myofibers shows elevated synthesis in response to exposure to high altitudes (5) or intense endurance training under reduced oxygen pressures (4-6). Fraser et al (7) now report, on page 2977 in this issue of PNAS, that the hypoxiatolerant common carp (Cyprinus carpio) has Mb not only in muscle but also in other metabolically active tissues that include liver, brain, and gills.…”

“…The Ngb appears to mediate the delivery of oxygen to the mitochondria in the photoreceptor cells. Fraser et al (7) find that 3 days of exposure to hypoxia (Ϸ10% normoxia) resulted in a 4-fold increase in mRNA expression of Myg-1 in carp muscle but only at the stressful temperature of 30°C. Hypoxic exposure of fish at 17°C yielded no Myg-1 elevation in muscle at all.…”

“…Fraser et al (7) have addressed this question by identifying two unique Mbs in carp tissue, Myg-1 and -2. Myg-1 is expressed not only in muscle but also in liver, kidney, and gill tissue.…”

Globins in Caenorhabditis elegans

“…The characterization of new vertebrate globins led to the conclusion that not all O 2 -binding proteins function in ways directly related to cellular oxygenation. One example is the discovery of two Mb isoforms in metabolically active tissues other than cardiac and skeletal muscle in the hypoxia tolerant carp (Cyprinus carpio) (39)(40)(41). Although the Mb isoform that is expressed in the gills, liver, kidney, and muscle (cMb1) is upregulated under hypoxic conditions, the other isoform that occurs only in the brain (cMb2) is not.…”

Vitreoscilla Hemoglobin (VHb) Overexpression Increases Hypoxia Tolerance in Zebrafish (Danio rerio)

“…Myoglobin and hemoglobin are induced by hypoxia or ischemia Vogt et al 2001;Nitta et al 2003). In a hypoxia-tolerant fish model, the common carp (Cyprinus carpio L.), ectopic expression of the Mb gene was shown to be substantially enhanced in nonmuscle tissues such as the liver, gills, and brain (Fraser et al 2006). Therefore, transfer of specific globin genes to hosts could improve the hypoxia tolerance in vertebrates (Yoshizaki et al 1991;Khan et al 2006).…”