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Haptoglobin, a hemoglobin-binding plasma protein, is present in bony fish and mammals but not in frog and chicken.

ABSTRACT: Hemoglobin (Hb) released from erythrocytes may cause oxidation of lipids and proteins. Haptoglobin (Hp), which occurs in the plasma of all mammals, binds free Hb and inhibits its oxidative activity. It is not known whether this protective protein also exists in lower vertebrates. By analyzing available genomic sequences, we have found that bony fish, but not more primitive animals, have a gene coding for a protein homologous to mammalian Hp. Furthermore, we show that this protein is present in the plasma of Japanese pufferfish (Takifugu rubripes) and that it binds Hb. These results, together with a phylogenetic analysis, suggest that Hp evolved from a complement-associated protein (mannose-binding lectin-associated serine proteinase, MASP), with the emergence of fish. Surprisingly, we found that both chicken (Gallus gallus) and the Western clawed frog (Xenopus tropicalis) lack the Hp gene. In chicken plasma, however, we identified a different type of Hb-binding protein, PIT54, which has been reported to be a potent antioxidant. PIT54 is a soluble member of the family of scavenger receptor cysteine-rich proteins, and we found that its gene exists only in birds. We also show that the plasma of ostrich (Strutio camelus), a primitive bird, contains both PIT54 and Hp. Collectively, our data suggest that PIT54 has successively taken over the function of Hp during the evolution of the avian lineage and has completely replaced the latter protein in chicken.

SUBMITTER: Wicher KB

PROVIDER: S-EPMC1449665 | biostudies-literature | 2006 Mar

REPOSITORIES: biostudies-literature

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Haptoglobin, a hemoglobin-binding plasma protein, is present in bony fish and mammals but not in frog and chicken.

Wicher Krzysztof B KB Fries Erik E

Proceedings of the National Academy of Sciences of the United States of America 20060306 11

Hemoglobin (Hb) released from erythrocytes may cause oxidation of lipids and proteins. Haptoglobin (Hp), which occurs in the plasma of all mammals, binds free Hb and inhibits its oxidative activity. It is not known whether this protective protein also exists in lower vertebrates. By analyzing available genomic sequences, we have found that bony fish, but not more primitive animals, have a gene coding for a protein homologous to mammalian Hp. Furthermore, we show that this protein is present in t ...[more]

PMID: 16537503

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Project description:BACKGROUND:Preclinical studies have evaluated haptoglobin (Hp) polymers from pooled human plasma as a therapeutic protein to attenuate toxic effects of cell-free hemoglobin (Hb). Proof of concept studies have demonstrated efficacy of Hp in hemolysis associated with transfusion and sickle cell anemia. However, phenotype-specific Hp products might be desirable to exploit phenotype specific activities of Hp 1-1 versus Hp 2-2, offering opportunities for recombinant therapeutics. Prohaptoglobin (proHp) is the primary translation product of the Hp mRNA. ProHp is proteolytically cleaved by complement C1r subcomponent-like protein (C1r-LP) in the endoplasmic reticulum. Two main allelic Hp variants, HP1 and HP2 exist. The larger HP2 is considered to be the ancestor variant of all human Hp alleles and is characterized by an α2-chain, which contains an extra cysteine residue that pairs with additional α-chains generating multimers with molecular weights of 200-900 kDa. The two human HP1 alleles (HP1F and HP1S) differ by a two-amino-acid substitution polymorphism within the α-chain and are derived from HP2 by recurring exon deletions. RESULTS:In the present study, we describe a process for the production of recombinant phenotype specific Hp polymers in mammalian FS293F cells. This approach demonstrates that efficient expression of mature and fully functional protein products requires co-expression of active C1r-LP. The functional characterization of our proteins, which included monomer/polymer distribution, binding affinities as well as NO-sparing and antioxidant functions, demonstrated that C1r-LP-processed recombinant Hp demonstrates equal protective functions as plasma derived Hp in vitro as well as in animal studies. CONCLUSIONS:We present a recombinant production process for fully functional phenotype-specific Hp therapeutics. The proposed process could accelerate the development of Hb scavengers to treat patients with cell-free Hb associated disease states, such as sickle cell disease and other hemolytic conditions.

Dataset Information

Haptoglobin, a hemoglobin-binding plasma protein, is present in bony fish and mammals but not in frog and chicken.

Publications

Haptoglobin, a hemoglobin-binding plasma protein, is present in bony fish and mammals but not in frog and chicken.

Similar Datasets

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