title: Emergence of the acute-phase protein hemopexin in jawed vertebrates.
abstract: When released from damaged erythrocytes free heme not only provides a source of iron for invading bacteria but also highly toxic due to its ability to catalyze free radical formation. Hemopexin (Hx) binds free heme with very high-affinity and thus protects against heme toxicity, sequesters heme from pathogens, and helps conserve valuable iron. Hx is also an acute-phase serum protein (APP), whose expression is induced by inflammation. To date Hx has been identified as far back in phylogeny as bony fish where it is called warm-temperature acclimation-related 65 kDa protein (WAP65), as serum protein levels are increased at elevated environmental temperatures as well as by infection. During analysis of nurse shark (Ginglymostoma cirratum) plasma we isolated a Ni(2+)-binding serum glycoprotein and characterized it as the APP Hx. We subsequently cloned Hx from nurse shark and another cartilaginous fish species, the little skate Leucoraja erinacea. Functional analysis showed shark Hx, like that of mammals, binds heme but is found at unusually high levels in normal shark serum. As an Hx orthologue could not be found in the genomes of jawless vertebrates or lower deuterostomes it appears to have arisen just prior to the emergence of jawed vertebrates, coincident with the second round of genome-wide duplication and the appearance of tetrameric hemoglobin (Hb).
authors.affiliation: Department of Microbiology & Immunology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA. helen.dooley@pfizer.com
authors.forename: Helen
authors.initials: H
authors.lastname: Dooley
authors.forename: E Bryan
authors.initials: EB
authors.lastname: Buckingham
authors.forename: Michael F
authors.initials: MF
authors.lastname: Criscitiello
authors.forename: Martin F
authors.initials: MF
authors.lastname: Flajnik
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D015152:Blotting, Northern; D005399:Fishes / Q000502:physiology*; D006466:Hemopexin / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment; D012754:Sharks / Q000502:physiology*; D012860:Skates, Fish
chemical_list: D006466:Hemopexin