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 is 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 Ni2+-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 haemoglobin (Hb).

Modulation of warm-temperature-acclimation-associated 65-kDa protein genes (Wap65-1 and Wap65-2) in mud loach (Misgurnus mizolepis, Cypriniformes) liver in response to different stimulatory treatments

“…Furthermore, the expression of this glycoprotein gene is readily modulated by environmental perturbations, including exposure to heavy metals [9,10] and other xenobiotic or toxic compounds [11e13]. Recent phylogenetic studies have also indicated that the fish Wap65 genes have undergone subfunctionalization and/or neofunctionalization via a lineage-specific genome-wide duplication, so that positive Darwinian selection might have been an important factor in the evolution of the fish Wap65 genes [7,14].…”

A Proteomic Approach to Investigate Myocarditis

“…A preliminary speculation on identified proteins might involve the function of hempopexin. As shown by literature data (Dooley H et al, 2010, : Mauk MR et al, 2011, Larsen R et al,2010, hemopexin is a serum protein with the very well known function of scavenging the h e m e r e l e a s e d o r l o s t b y t h e t u r n o v e r o f heme proteins such as haemoglobin or by haemolysis caused by parasitic infection, and thus protects the body from the oxidative damage that free heme can cause (Larsen R et al,2010). Myocarditis itself it's not related to haemolysis phenomena, but some viral infections may cause it, therefore, finding a very high level of hempoxin in a myocarditis affected patient might be a putative marker of the inflammation itself (quite common are in fact viral myocarditis).…”

“…Thanks to this approach, we could identify many proteins differently expressed in the two sera. Among identified proteins, hemopexin (Dooley H et al, 2010) , complement C3 (Adamsson Eryd S et al, 2011, Onat A et al, 2011, plasma kallikrein (Kolte D et al,2011) are undoubtedly related to inflammatory events and most interestingly they resulted clearly over expressed in the pathologic sample. A preliminary speculation on identified proteins might involve the function of hempopexin.…”

Genomic Organization and Isoform-Dependent Expression Patterns of Wap65 genes in Various Tissues during Immune Challenges in the Mud Loach Misgurnus mizolepis

“…3). Doses of immune-stimulating agents (ET and LPS) used in this study tion of ray-finned fish (Dooley et al, 2010;Sarropoulou and Fernandes, 2011); thus, such an inter-isoform difference in exon-intron organization may be a more recent lineage-or species-specific event. Besides the difference in exon-intron organization, the Wap65 gene is also known to have undergone species-specific gene duplication (i.e., intra-chromosomal amplification), resulting in gene copy number variability among species as evidenced by the four tandem copies of the Wap65-1 gene (whereas only one copy of Wap65-2 isoform) in the catfish (Ictalurus punctatus) genome (Sha et al, 2008).…”