Acellular Invertebrate Hemoglobins as Model Therapeutic Oxygen Carriers: Unique Redox Potentials

Abstract

Natural acellular polymeric hemoglobins (Hb) provide oxygen transport and delivery within many terrestrial and marine invertebrate organisms. It has been our premise that these natural acellular Hbs may serve as models of therapeutic hemoglobin-based oxygen carriers (HBOC). Our attention has focused on the acellular Hb from the terrestrial invertebrate, Lumbricus terrestris (Lt), which possesses a unique hierarchical structure and a unique ability to function extracellularly without oxidative damage. Lumbricus Hb and Arenicola Hb are resistant to autoxidation, chemical oxidation by potassium ferricyanide, and have little or no capacity to transfer electrons to Fe(+3)-complexes at 37 degrees C. An understanding of how these invertebrate acellular oxygen carriers maintain their structural integrity and redox stability in vivo is vital for the design of a safe and effective red cell substitute. We report here a positive redox potential for these giant hemoglobins that may lie at the basis for its resistance to oxidation.

Characteristic emission in glutaraldehyde polymerized hemoglobin

“…For example, Polyheme s and Hemopure s developed, respectively, by formal Northfield Laboratory and Biopure Corp are low oxygen affinity, large molecular size polymers. The large body of research has been conducted to relate structural characteristics of modified Hb to its biological functions by spectroscopic techniques, including absorption and fluorescence [6][7][8][9]. The fluorescence spectroscopy, however, has limitation due to the weak intrinsic emissions from Hb.…”

Ferric species of the giant extracellular hemoglobin of Glossoscolex paulistus as function of pH: An EPR study on the irreversibility of the heme transitions

“…The oxygen binding properties of the giant extracellular hemoglobin of Oligobrachia mashikoi, for instance, are regulated by divalent cations, which preferentially bind to the oxy-form (Aki et al, 2007). Significant effort to employ this class of hemoglobin as blood substitute, i.e., artificial oxygen carrier has been developed (Harrington et al, 2007). Indeed, the high autoxidation resistance, which is found in the giant extracellular hemoglobins, is an important prerequisite to this kind of physiological application (Harrington et al, 2007;Rousselot et al, 2006;Hirsch et al, 1997).…”

“…Significant effort to employ this class of hemoglobin as blood substitute, i.e., artificial oxygen carrier has been developed (Harrington et al, 2007). Indeed, the high autoxidation resistance, which is found in the giant extracellular hemoglobins, is an important prerequisite to this kind of physiological application (Harrington et al, 2007;Rousselot et al, 2006;Hirsch et al, 1997). Although nonvertebrates are phylogenetically more primitive than vertebrates, the high variability encountered in their hemoglobins reflects specialization and adaptation to a greater range of operating conditions than those found in vertebrates (Weber and Vinogradov, 2001).…”

Giant Extracellular Hemoglobin of Glossoscolex paulistus: An excellent Prototype of Biosensor and Blood Substitute

“…Natural acellular polymeric hemoglobins (Hb) provide oxygen transport and delivery within many terrestrial and marine invertebrate organisms. These natural acellular Hbs may serve as models of therapeutic hemoglobin-based oxygen carriers (HBOC) (Harrington et al, 2007). For instance, acellular Hb from the terrestrial invertebrate Lumbricus terrestris (Lt) possesses a unique hierarchical structure and a peculiar ability to function extracellularly without oxidative damage.…”

“…An understanding of how these invertebrate acellular oxygen carriers maintain their structural integrity and redox stability in vivo is vital for the design of a safe and effective red cell substitute. In fact, this hemoglobin presents positive redox potential (Harrington et al, 2007). Homotropic and heterotropic allosteric interactions are important mechanisms that regulate protein function.…”