Hemopexin

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This article is about the hemopexin protein. For the family of proteins containing hemopexin-like repeats, see hemopexin family.
HPX
Identifiers
Aliases HPX, HX, hemopexin
External IDs OMIM: 142290 MGI: 105112 HomoloGene: 511 GeneCards: HPX
RNA expression pattern
PBB GE HPX 210013 at tn.png

PBB GE HPX 39763 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000613

NM_017371

RefSeq (protein)

NP_000604.1

NP_059067.2

Location (UCSC) Chr 11: 6.43 – 6.44 Mb Chr 7: 105.59 – 105.6 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Hemopexin (or haemopexin; HPX), also known as beta-1B-glycoprotein is a protein that in humans is encoded by the HPX gene[3][4][5] and belongs to hemopexin family of proteins.[6] Hemoglobin and its scavenger protein hemopexin (Hx) associate with HDL and influence the inflammatory properties of HDL. In addition it can also be said that HDL from Hx-null mice is proinflammatory. Moreover, Hemopexin deficiency is associated with various other inflammatory diseases such as septic shock and experimental autoimmune encephalomyelitis.[7]

Cloning, expression and discovery[edit]

Takahashi et al. (1985) determined that human plasma beta-glycoprotein hemopexin consists of a single polypeptide chain of 439 amino acids residues with six intrachain disulphide bridges and has a molecular mass of approximately 63 kD. The amino-terminal threonine residue is blocked by an O-linked galactosamine oligosaccharide, and the protein has five glucosamine oligosaccharides N-linked to the acceptor sequence Asn-X-Ser/Thr. The 18 tryptophan residues are arranged in four clusters, and 12 of the tryptophans are conserved in homologous positions. Computer-assisted analysis of the internal homology in amino acid sequence suggested duplication of an ancestral gene thus indicating that hemopexin consists of two similar halves.[8] Altruda et al. (1988) demonstrated that the hemopexin gene spans approximately 12 kb and is interrupted by 9 exons. The demonstration shows direct correspondence between exons and the 10 repeating units in the protein. As the introns were not placed randomly; they fell in the center of the region of amino acid sequence homology in strikingly similar locations in 6 of the 10 units and in a symmetric position in each half of the coding sequence. From these observations, Altruda et al. (1988) concluded that the gene evolved through intron-mediated duplications of a primordial sequence to a 5-exon cluster.[9]

Mapping of hemopexin gene[edit]

Cai and Law (1986) prepared a cDNA clone for hemopexin ,by Southern blot analysis of human/hamster hybrids containing different combinations of human chromosomes, assigned the hemopexin gene to human chromosome 11. Law et al. (1988) assigned the hemopexin gene to 11p15.5-p15.4, the same location as that of the beta-globin gene complex by in situ hybridization.[10]

Function[edit]

Hemopexin binds heme with the highest affinity of any known protein. Its function is scavenging the heme released or lost by the turnover of heme proteins such as hemoglobin and thus protects the body from the oxidative damage that free heme can cause. In addition, hemopexin releases its bound ligand for internalisation upon interacting with a specific receptor situated on the surface of liver cells. This function of hemopexin is to preserve the body's iron.[11] Hemopexin, an acute phase protein, can downregulate the angiotensin (ang) II type 1 receptor (AT1-R) in vitro.[12]

Hx-dependent uptake of extracellular heme can lead to the deactivation of Bach1 repression which leads to the transcriptional activation of antioxidant heme oxygenase-1 gene. There are certain levels of circulating Hx which implicates in the prognosis for patients with septic shock. Therefore it can also be said that, Hx therapy has been shown to be beneficial in cardiovascular disease, cerebral ischemic injury, and experimental autoimmune encephalomyelitis.[13]

Clinical significance[edit]

Its levels in serum reflect how much heme is present in the blood. Therefore, low hemopexin levels indicates that there has been significant degradation of heme containing compounds and hemopexin is made to scavenge any heme it can. Low hemopexin levels are one of the diagnostic features of an intravascular hemolytic anemia.[14]

Controversies[edit]

In past there have been reports showing from patients with sickle cell disease, spherocytosis, autoimmune hemolytic anemia, erythropoietic protoporphyria and pyruvate kinase deficiency which have been suggested that Haptoglobin (Hp) depletion in plasma occurs prior to the decline of hemopexin (Hx) concentrations (Muller-Eberhard et al., 1968). Heme released during oxidation of Hb to met-Hb or from heme saturated hepatocytes is bound by albumin and rapidly transferred to Hx, the plasma protein with the highest binding affinity for heme. Hx is glycoprotein produced by the liver with a plasma concentration of 1–2 mg/ml (Muller-Eberhard et al., 1968). Hx prevents heme's pro-oxidant and pro-inflammatory effects and it also promotes its detoxification, specifically when Hp concentrations are low or depleted in cases of severe or prolonged hemolysis. Hp and Hx, both are acute-phase proteins,induced during infection and inflammatory states to minimize tissue injury and facilitate tissue repair.The current review also suggests that the primary mechanisms by which Hp and Hx prevent heme toxicity prior to monocyte or macrophage clearance, it also critically evaluate the difference in genetic phenotype function and describe the rationale for exogenous Hp and Hx as therapeutic proteins.[15]

Mutations[edit]

Deletion of the hemopexin or heme oxygenase-2 gene can aggravates brain injury followed by stroma-free hemoglobin-induced intracerebral haemorrhage.[16]

Differential transcriptional pattern of hemopexin gene[edit]

The expression of the human hemopexin gene in different human tissues and cell lines was carried out by using the specific cDNA probe. From the results obtained it can be concluded that this gene is expressed in liver and, in lower amount, in hepatoma cell lines but not in kidney, spleen, placental cells, and in HeLa, fibroblast cell lines.By S1 mapping it can also said that the transcription initiation site in hepatic cells is 28 base pairs upstream from the AUG initiation codon of the hemopexin gene.[17]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ "Entrez Gene: HPX hemopexin". 
  4. ^ Altruda F, Poli V, Restagno G, Silengo L (1988). "Structure of the human hemopexin gene and evidence for intron-mediated evolution". Journal of Molecular Evolution. 27 (2): 102–8. doi:10.1007/BF02138368. PMID 2842511. 
  5. ^ Altruda F, Poli V, Restagno G, Argos P, Cortese R, Silengo L (June 1985). "The primary structure of human hemopexin deduced from cDNA sequence: evidence for internal, repeating homology". Nucleic Acids Research. 13 (11): 3841–59. doi:10.1093/nar/13.11.3841. PMC 341281Freely accessible. PMID 2989777. 
  6. ^ Bode W (June 1995). "A helping hand for collagenases: the haemopexin-like domain". Structure. 3 (6): 527–30. doi:10.1016/s0969-2126(01)00185-x. PMID 8590012. 
  7. ^ "Role of hemoglobin/heme scavenger protein hemopexin in atherosclerosis and inflammatory diseases". PMID 26339767. 
  8. ^ Online Mendelian Inheritance in Man (OMIM) Orthosatic intolerance -604715
  9. ^ Takahashi N, Takahashi Y, Putnam FW (January 1985). "Complete amino acid sequence of human hemopexin, the heme-binding protein of serum". Proceedings of the National Academy of Sciences of the United States of America. 82 (1): 73–7. doi:10.1073/pnas.82.1.73. PMC 396973Freely accessible. PMID 3855550. 
  10. ^ Online Mendelian Inheritance in Man (OMIM) Hemopexin -142290
  11. ^ Tolosano E, Altruda F (April 2002). "Hemopexin: structure, function, and regulation". DNA and Cell Biology. 21 (4): 297–306. doi:10.1089/104454902753759717. PMID 12042069. 
  12. ^ Krikken JA, Lely AT, Bakker SJ, Borghuis T, Faas MM, van Goor H, Navis G, Bakker WW (March 2013). "Hemopexin activity is associated with angiotensin II responsiveness in humans". Journal of Hypertension. 31 (3): 537–41. doi:10.1097/HJH.0b013e32835c1727. PMID 23254305. 
  13. ^ Mehta NU, Reddy ST (October 2015). "Role of hemoglobin/heme scavenger protein hemopexin in atherosclerosis and inflammatory diseases". Current Opinion in Lipidology. 26 (5): 384–7. doi:10.1097/MOL.0000000000000208. PMC 4826275Freely accessible. PMID 26339767. 
  14. ^ Hoffbrand A, Moss P, Pettit J (2006). Essential Haematology (5th ed.). Oxford: Blackwell Publishing. p. 60. ISBN 978-1-4051-3649-5. 
  15. ^ Schaer DJ, Vinchi F, Ingoglia G, Tolosano E, Buehler PW (2014). "Haptoglobin, hemopexin, and related defense pathways-basic science, clinical perspectives, and drug development". Frontiers in Physiology. 5: 415. doi:10.3389/fphys.2014.00415. PMC 4211382Freely accessible. PMID 25389409. 
  16. ^ Ma B, Day JP, Phillips H, Slootsky B, Tolosano E, Doré S (2016). "Deletion of the hemopexin or heme oxygenase-2 gene aggravates brain injury following stroma-free hemoglobin-induced intracerebral hemorrhage". Journal of Neuroinflammation. 13: 26. doi:10.1186/s12974-016-0490-1. PMC 4736638Freely accessible. PMID 26831741. 
  17. ^ Poli V, Altruda F, Silengo L (1986). "Differential transcriptional pattern of the hemopexin gene". The Italian Journal of Biochemistry. 35 (5): 355–60. PMID 3026994. 

Further reading[edit]

External links[edit]

See also[edit]