Tissue-restricted myoglobin expression within vertebrates

Introduction Myoglobin is a monomeric hemoprotein that has captivated the interests of scientists and physicians for the past 60 years. It is a cytoplasmic hemoprotein that is expressed primarily within cells of striated muscle lineages of vertebrates (i.e. cardiomyocytes and oxidative skeletal muscle myofibers). Previous biophysical, cellular, molecular, pharmacological and physiological investigations have elucidated important findings regarding myoglobin’s structure and functional role within cardiac and skeletal muscles of various vertebrate species (Flogel et al., 2004; Flogel et al., 2005; Flogel et al., 2001; Garry et al., 1998; Godecke et al., 1999; Godecke et al., 2003; Grange et al., 2001; HendgenCotta et al., 2008; Kanatous et al., 1999; Kanatous et al., 2002; Kanatous et al., 2008; Kendrew, 1963; Kendrew et al., 1958; Kendrew et al., 1960; Kendrew et al., 1954; Mammen et al., 2003; Meeson et al., 2001; Noren et al., 2001; Noren et al., 2005; Takahashi et al., 2000; Wittenberg, 1965; Wittenberg, 1966; Wittenberg, 1970; Wittenberg, 2007; Wittenberg and Wittenberg, 1987; Wittenberg and Wittenberg, 2003; Wittenberg and Wittenberg, 2007; Wittenberg et al., 1975; Wittenberg et al., 1985). These studies have clearly demonstrated myoglobin’s role as an oxygen (O2) storage hemoprotein, facilitator of intracellular O2 transport, and modulator of O2 and nitric oxide (NO) homeostasis. As there have been several recent reviews that have focused on the functional roles of myoglobin, the current review will instead highlight and summarize studies undertaken to enhance our understanding of the mechanisms regulating myoglobin expression. Myoglobin genomic organization and gene structure Myoglobin is a member of the globin family, which includes cytoglobin, hemoglobin and neuroglobin. Myoglobin is phylogenetically most similar to cytoglobin, another monomeric hemoprotein that is ubiquitously expressed in all vertebrate tissues (Burmester et al., 2002; Singh et al., 2009; Trent and Hargrove, 2002). Myoglobin, cytoglobin and hemoglobin are believed to have shared a common ancestral globin more than 500 million years ago (Burmester et al., 2002). The genomic structure of the myoglobin gene has been extensively studied in a variety of species, including the Grey seal (Halichoerus grypus), human (Homo sapiens), mouse (Mus musculus) and sperm whale (Physeter catodon) (Blanchetot et al., 1986; Weller et al., 1986; Wittenberg and Wittenberg, 1989). These studies have demonstrated a considerable homology among various species in regards to the genomic structure of the myoglobin gene. The overall genomic structure of the myoglobin gene is relatively simple and is composed of only three exons and two introns. Among all the species studied, exon 2 encodes the heme-binding domain, which is responsible for the reversible binding to various ligands (i.e. O2, NO, free radicals, etc.) (Blanchetot et al., 1986).