Haptoglobin (Hp) belongs to the family of acute-phase plasma proteins and represents the most important plasma detoxifier of hemoglobin (Hb). The basic Hp molecule is a tetrameric protein built by two α/β dimers. Each Hp α/β dimer is encoded by a single gene and is synthesized as a single polypeptide. Following post-translational protease-dependent cleavage of the Hp polypeptide, the α and β chains are linked by disulfide bridge(s) to generate the mature Hp protein. As human Hp gene is characterized by two common Hp1 and Hp2 alleles, three major genotypes can result (i.e., Hp1-1, Hp2-1, and Hp2-2). Hp regulates Hb clearance from circulation by the macrophage-specific receptor CD163, thus preventing Hb-mediated severe consequences for health. Indeed, the antioxidant and Hb binding properties of Hp as well as its ability to stimulate cells of the monocyte/macrophage lineage and to modulate the helper T-cell type 1 and type 2 balance significantly associate with a variety of pathogenic disorders (e.g., infectious diseases, diabetes, cardiovascular diseases, and cancer). Alternative functions of the variants Hp1 and Hp2 have been reported, particularly in the susceptibility and protection against infectious (e.g., pulmonary tuberculosis, HIV, and malaria) and non-infectious (e.g., diabetes, cardiovascular diseases and obesity) diseases. Both high and low levels of Hp are indicative of clinical conditions: Hp plasma levels increase during infections, inflammation, and various malignant diseases, and decrease during malnutrition, hemolysis, hepatic disease, allergic reactions, and seizure disorders. Of note, the Hp:Hb complexes display heme-based reactivity; in fact, they bind several ferrous and ferric ligands, including O2, CO, and NO, and display (pseudo-)enzymatic properties (e.g., NO and peroxynitrite detoxification). Here, genetic, biochemical, biomedical, and biotechnological aspects of Hp are reviewed.

di Masi, A., De Simone, G., Ciaccio, C., D'Orso, S., Coletta, M., Ascenzi, P. (2020). Haptoglobin: from hemoglobin scavenging to human health. MOLECULAR ASPECTS OF MEDICINE, 73 [10.1016/j.mam.2020.100851].

Haptoglobin: from hemoglobin scavenging to human health

Ciaccio, Chiara;Coletta, Massimo;
2020-01-01

Abstract

Haptoglobin (Hp) belongs to the family of acute-phase plasma proteins and represents the most important plasma detoxifier of hemoglobin (Hb). The basic Hp molecule is a tetrameric protein built by two α/β dimers. Each Hp α/β dimer is encoded by a single gene and is synthesized as a single polypeptide. Following post-translational protease-dependent cleavage of the Hp polypeptide, the α and β chains are linked by disulfide bridge(s) to generate the mature Hp protein. As human Hp gene is characterized by two common Hp1 and Hp2 alleles, three major genotypes can result (i.e., Hp1-1, Hp2-1, and Hp2-2). Hp regulates Hb clearance from circulation by the macrophage-specific receptor CD163, thus preventing Hb-mediated severe consequences for health. Indeed, the antioxidant and Hb binding properties of Hp as well as its ability to stimulate cells of the monocyte/macrophage lineage and to modulate the helper T-cell type 1 and type 2 balance significantly associate with a variety of pathogenic disorders (e.g., infectious diseases, diabetes, cardiovascular diseases, and cancer). Alternative functions of the variants Hp1 and Hp2 have been reported, particularly in the susceptibility and protection against infectious (e.g., pulmonary tuberculosis, HIV, and malaria) and non-infectious (e.g., diabetes, cardiovascular diseases and obesity) diseases. Both high and low levels of Hp are indicative of clinical conditions: Hp plasma levels increase during infections, inflammation, and various malignant diseases, and decrease during malnutrition, hemolysis, hepatic disease, allergic reactions, and seizure disorders. Of note, the Hp:Hb complexes display heme-based reactivity; in fact, they bind several ferrous and ferric ligands, including O2, CO, and NO, and display (pseudo-)enzymatic properties (e.g., NO and peroxynitrite detoxification). Here, genetic, biochemical, biomedical, and biotechnological aspects of Hp are reviewed.
2020
Pubblicato
Rilevanza internazionale
Recensione
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
English
Con Impact Factor ISI
Disease
Function
Haptoglobin
Hemoglobin
Structure
di Masi, A., De Simone, G., Ciaccio, C., D'Orso, S., Coletta, M., Ascenzi, P. (2020). Haptoglobin: from hemoglobin scavenging to human health. MOLECULAR ASPECTS OF MEDICINE, 73 [10.1016/j.mam.2020.100851].
di Masi, A; De Simone, G; Ciaccio, C; D'Orso, S; Coletta, M; Ascenzi, P
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
2020 Haptoglobin Review.pdf

solo utenti autorizzati

Tipologia: Versione Editoriale (PDF)
Licenza: Copyright dell'editore
Dimensione 9.84 MB
Formato Adobe PDF
9.84 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/255176
Citazioni
  • ???jsp.display-item.citation.pmc??? 40
  • Scopus 70
  • ???jsp.display-item.citation.isi??? 60
social impact