Disease relevance of HP

• Ectopic expression and activation of wild-type STAT3 or STAT3SA in HepG2 hepatoma cells similarly enhance transcription through the IL-6-response element of the HP promoter [1].
• Furthermore, an association between HP type and infarction size was observed, HP 2-2 being associated with smaller infarctions [2].
• Close linkage of HP on chromosome 16 and MEN-2A is excluded [3].
• In an earlier paper, positive but nonsignificant lod scores were found in pair-wise linkage tests between multiple endocrine neoplasia type 2A (MEN-2A) and both the haptoglobin (HP) locus on chromosome 16 and group-specific component (GC) locus on chromosome 4 [3].
• This specific receptor-ligand interaction leading to removal from plasma of the Hp-Hb complex-but not free Hp or Hb-now explains the depletion of circulating Hp in individuals with increased intravascular hemolysis [4].

Psychiatry related information on HP

• The disorders in Hp and Tf circulating levels are highly sensitive to (83%) and specific for (100%) melancholia as opposed to the healthy state [5].
• We studied the pattern of acute-phase proteins (orosomucoid, C-reactive protein, and haptoglobin) in hepatocellular deficiency due to chronic alcohol consumption, characterized by a decrease in serum transferrin concentration [6].
• Serum and cerebrospinal fluid (CSF) from 22 ambulatory and 10 institutionalised patients with Alzheimer's disease (AD) and 22 age-matched controls were assayed nephelometrically for concentrations of IgG, IgA, IgM, haptoglobin, transferrin, prealbumin and albumin [7].
• The present study shows that the pattern of appearance of serum haptoglobin during the neonatal period is associated with ACP1 phenotype suggesting some important function of this polymorphic enzyme in human development [8].
• On the other hand, the Hp 2-2 value is not increased in the systematic schizophrenias, but it displays a relative overplus in the unsystematic forms [9].

High impact information on HP

• Haptoglobin phenotype and vascular complications in patients with diabetes [10].
• Transgenic mice were generated that expressed a human collagenase transgene in their lungs under the direction of the haptoglobin promoter [11].
• Comparison of serum enzyme activities in the remaining 374 patients confirmed that Hp 2-2 patients had significantly higher total creatine kinase, creatine kinase isoenzyme MB fraction, aspartate aminotransferase, and lactate dehydrogenase peak levels [12].
• Effect of the haptoglobin phenotype on the size of a myocardial infarct [12].
• Complexes of haemoglobin and multimeric haptoglobin (the 2-2 phenotype) exhibit higher functional affinity for CD 163 than do complexes of haemoglobin and dimeric haptoglobin (the 1-1 phenotype) [13].

Chemical compound and disease context of HP

• In patients with acute myocardial infarction, the haptoglobin (HP) groups were found to be associated with serum cholesterol levels [2].
• Haptoglobin (Hp) is a glycoprotein involved in the acute phase response to inflammation [14].
• METHODS: Haptoglobin phenotypes were determined in serum of 128 breast cancer patients (familial, n=42; nonfamilial, n=86) and in controls (n=200) by vertical polyacrylamide gel electrophoresis [15].
• OBJECTIVE: We investigated the effect of a diet with a high content of sucrose or artificial sweeteners on the inflammatory markers CRP, haptoglobin, and transferrin in overweight subjects [16].
• The purpose of this study was to evaluate the influence of three sialic acid rich glycoproteins (orosomucoid, haptoglobin, and alpha1-antitrypsin) on the relationship between S-TSA and carotid atherosclerosis [17].

Biological context of HP

• The allele frequency of HP A*2SS, which is common in the European population, is less frequent than HP A*2V1 in the Japanese population [18].
• Of these three markers, only the HP locus was found to be codeleted with the TAT locus on the del(16) chromosome [19].
• The DNA sequence(s) responsible for the normally high level of HP expression in liver either reside outside the 3.3-kb regulatory region of the HP chimeric gene or this region contains a suppressor sequence affecting tissue specific expression in the liver [20].
• A significant decrease in HP 2-1 frequency was found, suggesting protection for heterozygotes in both DM and DR (with a relative risk of about 0.31) [21].
• APRT was found to be distal to HP and FRA16D and was localized at 16q24, making the gene order cen-FRA16B-HP-FRA16D-APRT-qter [22].

Anatomical context of HP

• A subclone of APRT and a cDNA clone of HP were used for molecular hybridization to DNA from mouse-human hybrid cell lines containing specific chromosome 16 translocations [22].
• The Western blotting technique was used to achieve the transfer of HP bands from the gels to the nitrocellulose membranes [23].
• Fibroblast cell cultures from two Hp2/Hp1 heterozygotes were fused to mouse cells to obtain cell lines retaining a human chromosome 16 on which the haptoglobin gene cluster is located [24].
• Haptoglobin (Hp) is unusual in that it is cleaved in the endoplasmic reticulum before it enters the Golgi [25].
• We report that purified fluorescein-labeled haptoglobin 1-1 binds to THP1 and U937 promonocytic cell lines, to monocytes, to granulocytes, and to a subset of CD8+ T cells and to NK cells [26].

Associations of HP with chemical compounds

• To assess the role of STAT3 in the transcriptional control of the HP promoter, we applied two mutant forms of STAT3: one with a deletion of the carboxyl-terminal 55 amino acid residues, STAT3Delta55C, and the other with a substitution of serine 727 to alanine, STAT3SA [1].
• Heterozygotes (HP 2-1) showed serum cholesterol levels significantly higher (p less than 0.0001) than those of patients with HP 1-1 or HP 2-2 [2].
• Blood and serum samples from random individuals of Madras City, South India, were screened for ESD and HP polymorphisms using mixed starch agarose gel electrophoresis and polyacrylamide slab gel electrophoresis respectively [27].
• Enzyme immunoassay was found to be clearly more sensitive than o-dianisidine or o-tolidine in detecting HP bands from diluted serum samples [23].
• Binding to THP1 and U937 cells could be inhibited by preincubation with nonfluoresceinated haptoglobin and by fibrinogen, but not by albumin, transferrin, or alpha1-acid glycoprotein [26].

Physical interactions of HP

• Based on these results, we propose that Hpr mediates the high affinity binding of TLF-1 to T. b. brucei through a haptoglobin-like receptor [28].
• Its function has remained unknown until recently when CD163 was identified as the endocytic receptor binding hemoglobin (Hb) in complex with the plasma protein haptoglobin (Hp) [4].
• We have previously shown that Hp interacts with the beta2-integrin CD11b/CD18 [29].
• Haptoglobin polymorphisms result in proteins with altered haemoglobin-binding capacity and different antioxidant, iron-recycling, and immune functions [30].
• The ApoA-I structure was analyzed to detect the site bound by Hpt [31].

Regulatory relationships of HP

• The carboxyl-terminal region of STAT3 controls gene induction by the mouse haptoglobin promoter [1].
• Haptoglobin inhibits lecithin-cholesterol acyltransferase in human ovarian follicular fluid [32].
• Haptoglobin type neither influences iron accumulation in normal subjects nor predicts clinical presentation in HFE C282Y haemochromatosis: phenotype and genotype analysis [33].
• We studied IL-6-induced secretion of the acute phase protein haptoglobin by hepatoma cells [34].
• Haptoglobin-hemoglobin complex formation promotes high affinity binding of hemoglobin to the macrophage scavenger receptor CD163 leading to endocytosis and degradation of the haptoglobin-hemoglobin complex [35].

Other interactions of HP

• Human genomic clones of the haptoglobin Hp1F and the "haptoglobin related' gene (Hpr) have been isolated [36].
• Binding of haptoglobin to purified CD11b/CD18 indicates that it binds directly to the receptor [26].
• The statistical analysis of our findings in comparison to the frequency of these genes in the general population does not reveal any correlation between the distribution of the Hp and Tf phenotypes and the disease [37].
• CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma [4].
• Gene frequencies are also given for previously described polymorphisms of 5 systems: haptoglobin, phosphoglucomutase 1, erythrocyte acid phosphatase, esterase D, and galactose-1-phosphate-uridyl-transferase [38].

Analytical, diagnostic and therapeutic context of HP

• Specific antibodies against the human haptoglobin (HP) alpha chain were raised and used for immunoblotting after isoelectric focusing to determine Hp alpha subtypes in a reproducible and simplified manner [18].
• Northern blot and primer elongation analyses with human liver RNA show that the haptoglobin gene Hp1F appears to be transcribed some 1000-fold less in fetal than in adult liver [36].
• Southern blot and PCR analyses have indicated that the individual with anhaptoglobinemia was homozygous for the gene deletion and that the gene deletion was included at least from the promoter region of Hp to Hpr alpha but not to Hpr beta (Hpdel) [39].
• Southern blot analysis indicated that 2 patients were homozygous for the deleted allele of the haptoglobin gene (Hp(del)) as reported previously [40].
• Tf and hp levels were significantly reduced in the HbSS groups relative to the control group [41].

References