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PubMed1998

Transport of intact porphyrin by HpuAB, the hemoglobin-haptoglobin utilization system of Neisseria meningitidis.

The meningococcal hemA gene was cloned and used to construct a porphyrin biosynthesis mutant. An analysis of the hemA mutant indicated that meningococci can transport intact porphyrin from heme (Hm), hemoglobin (Hb), and Hb-haptoglobin (Hp). By constructing a HemA- HpuAB- double mutant, we demonstrated that HpuAB is required for the transport of porphyrin from Hb and Hb-Hp.

Aldehyde Oxidoreductases↗
PubMed1990

Distinct regulation of the interleukin-1 and interleukin-6 response elements of the rat haptoglobin gene in rat and human hepatoma cells.

The transcription rate of the haptoglobin (Hp) gene is stimulated by interleukin-1 (IL-1), IL-6, and dexamethasone in rat hepatoma (H-35) cells. To identify the cis-acting regulatory elements responsive to these hormones, various lengths of 5' Hp gene-flanking regions, including the promoter, were inserted into chloramphenicol acetyltransferase gene expression vectors and transiently introduced into H-35 cells. The first 4 kb of 5' region mediated a severalfold increase in expression after treatment with IL-6 and dexamethasone. No response to IL-1 was detectable. When, however, upstream sequences were deleted to position -165 relative to the transcription start site, a significant stimulation by IL-1 was gained without appreciably affecting the IL-6 response. With the apparent removal of an inhibitory sequence, the promoter-proximal 165-bp region also displayed a severalfold enhanced response to the combination of dexamethasone, IL-1, and IL-6. The sequence from -165 to -147, termed the A-element, was found to be crucial for all hormone regulatory functions. Two copies of the A-element linked to a heterologous promoter responded to the three hormones, but to a lesser degree than in the Hp gene promoter context. The regulatory elements of the rat Hp gene were similarly active in human hepatoma cells. Optimal regulation by IL-6 in HepG2 cells was, however, independent of the A-element. The A-element functioned in these cells exclusively as an IL-1 response sequence. The results suggest that genomic sequences upstream of the rat Hp gene suppress the regulation by specific cytokines more prominently in transient expression assays than in the normal chromosomal context. Moreover, the functional comparison indicated that specific regulatory regions of the rat Hp gene do not function identically in different hepatic cell types.

Animals↗
PubMed1990

Structure, hormonal regulation, and identification of the interleukin-6- and dexamethasone-responsive element of the rat haptoglobin gene.

Hepatic expression of the haptoglobin (Hp) gene in mammalian species is stimulated severalfold during an acute-phase reaction. To identify the molecular mechanism responsible for this regulation, the single-copy rat Hp gene has been isolated. The genomic sequences showed a high degree of homology with the primate Hp gene. Activity of the rat Hp gene was increased in cultured liver cells by interleukin-1 (IL-1), IL-6, and glucocorticoids. The genomic Hp gene sequence spanning from -6500 to +6500, when transiently introduced into human hepatoma (HepG2) cells, directed IL-6- and dexamethasone-stimulated expression of rat Hp mRNA and protein. No response to IL-1 was detected, suggesting that the corresponding regulatory element(s) might lie outside of the tested gene sequences. An IL-6- and dexamethasone-responsive element has been localized to the promoter proximal region -146 to -55. Although the nucleotide sequences of this rat Hp gene region showed substantial divergence from that of the human gene, analysis of sequential 5' and 3' deletion constructs indicated an arrangement of functional IL-6 response elements in the rat Hp promoter sequence comparable to that of the human homolog. The magnitude of IL-6 regulation through the rat Hp gene promoter was severalfold lower than that of the human Hp gene. The reduced activity could be ascribed to a single-base difference in an otherwise conserved sequence corresponding to an active element in the human gene. The IL-6 response of the rat Hp element was improved severalfold by substituting that base with the human nucleotide.

Amino Acid Sequence↗
PubMed1979

Effects of gold, dapsone, and prednisone on serum C-reactive protein and haptoglobin and the erythrocyte sedimentation rate in rheumatoid arthritis.

Sequential measurements of serum C-reactive protein (CRP), serum haptoglobin (Hp), and erythrocyte sedimentation rate (ESR) were made in 209 patients with rheumatoid arthritis (RA); 78 of them were treated with gold, 71 with dapsone, and 60 with prednisone. The results were expressed as proportional changes in the measurements at 28-day intervals after treatment began. The period of study was 140 days. During treatment with gold and dapsone there were statistically significant gradual and progressive falls of similar magnitude in serum CRP and ESR. During treatment with prednisone serum CRP and ESR fell abruptly by 28 days and thereafter altered little. At 140 days prednisone had had the largest proportional effect on both measurements. During gold treatment the fall in serum Hp was similar to that of the ESR. In contrast, prednisone had little effect on Hp levels despite large falls in serum CRP and the ESR. Either prednisone stimulates Hp synthesis or the divergence is an expression of the difference in type of effect between gold and prednisone on RA. The effect of dapsone on serum Hp was large and progressive; it partly reflects haemolysis and, since the haemolysis was not progressive, partly improvement in the RA. The results show the relative efficacy of the drugs and suggest that dapsone may be a useful alternative treatment for RA.

Arthritis, Rheumatoid↗
PubMed2006

Haptoglobin polymorphism in a HIV-1 seropositive Brazilian population.

BACKGROUND: Haptoglobin (Hp) is a plasma protein with antioxidant and immunomodulatory properties. Three main genotypes/phenotypes (Hp1-1, Hp2-1, Hp2-2) show distinctive efficiencies in their activities and have been related to susceptibility and outcome in different diseases, including HIV infection. OBJECTIVE: To compare Hp genotype distribution between HIV-1 seropositive patients and healthy controls. METHODS: 387 Brazilian HIV-1 seropositive patients, subclassified as A, B, and C according to the Centers for Disease Control, were compared with 142 healthy controls. The influence of the polymorphism on iron status (serum iron, ferritin, transferrin, transferrin saturation), acute phase proteins (Hp, C reactive protein, fibrinogen, albumin), the HIV-1 viral load, and CD4+ T lymphocyte counts was examined. RESULTS: Apart from finding lower Hp concentrations among individuals with genotype Hp2-2, no other significant difference was observed. CONCLUSIONS: No association was found between Hp genotype and either HIV status or indices of HIV progression.

Adolescent↗
PubMed1970

Evaluation of haptoglobin phenotype 0-0 in cirrhotic and non-cirrhotic hospital populations.

The haptoglobin phenotypes of 3,332 individuals, consisting of 2,930 caucasians and 402 negroes living in the greater Boston area, were determined. Of these, 3,222 were hospitalized medical patients fully documented regarding diagnoses. One hundred and twentyeight of the total population studied were shown to exhibit starch gel anhaptoglobinaemia (3.7%). Re-evaluation on acrylamide gel of 118 0-0 samples revealed that the majority (94%) were derived from patients exhibiting hypohaptoglobinaemia rather than anhaptoglobinaemia.

Black People↗
PubMed1981

Phenotypic and quantitative relationship of red cell acid phosphatase with haemoglobin, haptoglobin, and G6PD phenotypes.

The phenotypic and quantitative relationship of red cell acid phosphatase with haemoglobin, haptoglobin, and G6PD phenotypes was investigated in three populations in the Sudan and one population in Nilgiris, India. No significant consistent association of red cell acid phosphatase phenotypes was observed with these polymorphisms. However, there was a lack of acid phosphatase AB in G6PD deficient subjects from Nilgiris. The relative quantitative expression of red cell acid phosphatase genes PA, PB, and PC was 1.0, 1.2, and 1.3, respectively. The red cell acid phosphatase activity was higher (15%) in the presence of raised haemoglobin A2 and in sickle cell anaemia (21%). Those with Hp2 had 18% higher level of acid phosphatase than those with Hp1. G6PD deficient subjects had a lower level of acid phosphatase activity (20%) than those with normal G6PD activity.

Acid Phosphatase↗
PubMed1985

Survey on haemoglobin variants, beta thalassaemia, glucose-6-phosphate dehydrogenase deficiency, and haptoglobin types in Turks from western Thrace.

A total of 102 apparently healthy and randomly selected Turks who either immigrated from Western Thrace or were still living there were studied for haemoglobin variants, high Hb A2 beta thalassaemia, G6PD deficiency, and haptoglobin types. The incidence of haemoglobins S and O Arab were 2.9 and 3.9% respectively. The incidence of high A2 beta thalassaemia was 10.8% and that of G6PD deficiency 5%. The gene frequencies of Hp1 and Hp2 were 0.326 and 0.674, respectively.

Adult↗
PubMed1988

Haptoglobin groups in motor neuron disease.

Haptoglobin (Hp) groups were investigated in 81 patients with motor neuron disease. A significant excess of heterozygotes was observed, accentuated among males and in the progressive spinal muscular atrophy subgroup. The results are discussed in terms of a possible influence of Hp in the immunological response.

Female↗
PubMed1976

Characterization of tryptic peptides from porcine haptoglobin light chain and an amino acid sequence.

The tryptic peptides derived from porcine haptoglobin light chains have been separated and characterized by composition, chromatography, electrophoretic mobility, and partial sequencing. Depending on homology with the corresponding human polypeptide, the amino acid sequence of the chain is proposed. Twenty differences from the human chain are indicated in the total of 84 residues.

Amino Acid Sequence↗
PubMed1988

Glycosylation of chicken haptoglobin: isolation and characterization of three molecular variants and studies of their distribution in hen plasma before and after turpentine-induced inflammation.

Chicken haptoglobin (Hp), a hemoglobin-binding protein isolated from chicken plasma, is composed of three molecular variants that react differently with concanavalin A (ConA). These glycosylation variants of chicken Hp have been isolated by affinity chromatography using Sepharose-bound ConA. They differ in their molecular weight, as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Analysis of the glycopeptides obtained after pronase digestion of these variants yielded two types of structures: one, reactive with ConA, corresponded to a biantennary N-linked carbohydrate unit and one, unreactive with ConA, corresponded to a triantennary unit. The strongly ConA-reactive Hp variant bears only two biantennary units and the nonreactive Hp variant bears only two triantennary units; the weakly reactive Hp variant bears equal amounts of both units. The distribution of Hp glycosylation variant does not show any significant difference when obtained from the plasma of laying hens before and after turpentine-induced inflammation.

Animals↗
PubMed2002

Haptoglobin reduces lung injury associated with exposure to blood.

The biological functions of the acute- phase protein haptoglobin (Hp) may be related to its ability to bind hemoglobin (Hb) or to modulate immune response. Hp is expressed at a high level in lung cells, yet its protective role(s) in the lung is not known. With the use of transgenic mice overexpressing Hp in alveolar macrophages, we demonstrated that Hp diminished Hb-induced lung injury when the lung was exposed to whole blood. In transgenic mouse lungs, Hb was more efficiently removed, and the induction of stress- responsive heme oxygenase-1 gene was significantly lower when compared with wild-type mice. At 24 h after blood treatment, the ferritin level that serves as an index for intracellular iron content was also lower in alveolar macrophages in transgenic mice than in wild-type mice. We propose that an Hp-mediated Hb catabolism process exists in alveolar macrophages. This process is likely coupled to an iron mobilization pathway and may be an efficient mechanism to reduce oxidative damage associated with hemolysis.

Animals↗
PubMedDate not supplied

Haptoglobin 1F allele frequency is high among indigenous populations in the state of Durango, Mexico.

We studied haptoglobin polymorphism in Mexican populations with high Indian ancestry living in isolated and urban areas in the state of Durango. Analysis with respect to the HP*1F and HP*1S allelic subtypes by isoelectric focusing showed unusually high HP*1F allele frequencies among urban (0.370) and isolated Mexican Indians (0.383). Comparison with other population studies demonstrated a geographical cline of the HP*1F allele increasing in the same direction of the HP*1 allele, while HP*1S frequency does not show racial differences.

Alleles↗
PubMedDate not supplied

Haptoglobin phenotypes in HIV-1-seropositive patients in Ghana: decreased risk for Hp0 individuals.

Plasma haptoglobin phenotypes were determined by polyacrylamide gel electrophoresis, followed by benzidine staining for 58 HIV-1 seropositive Ghanaians and 79 randomly selected age-matched controls. Hp0 was present in only 14% of HIV-1 seropositive individuals compared with more than 40% of the controls. The Hp0 individuals showed a highly significant reduced risk for HIV-1 infection (OR = 0. 21, 95% CI = 0.09-0.51, p = 0.0002). Hp0 may have a protective effect in HIV-1 infection.

Electrophoresis, Polyacrylamide Gel↗
PubMed2001

Involvement of phenotypes and serum levels of haptoglobin in the outcome of in vitro fertilization and embryo transfer.

Haptoglobin (Hp) possesses many functions in the immune system and angiogenesis as well as scavenging released hemoglobin, and thus it is speculated that Hp may also play a critical role in the reproductive process. To investigate the possible involvement of Hp in the outcome of in vitro fertilization and embryo transfer (IVF-ET), the serum Hp of 50 patients who underwent IVF-ET was analyzed by the Western blot method. The results showed a higher pregnancy rate in the patients with the Hp2-2 phenotype (38%) than in those with the Hp2-1 phenotype (16%) (p = 0.08), and the serum alpha 2 subunit levels in the patients who achieved pregnancy within four attempts at IVF-ET were higher than in the others (p < 0.05). The results of this study suggest that Hp is involved in the outcome of IVF-ET.

Adult↗
PubMedDate not supplied

The protein polymorphism of haptoglobin in Korean elite athletes.

OBJECTIVE: To investigate protein polymorphism of the haptoglobin (Hp) and the relationship between Hp phenotypes and anthropometric or biochemical parameters in elite Korean male athletes. MATERIALS AND METHODS: Serum samples were collected from 120 Korean male elite athletes. The Hp phenotypes were determined by polyacrylamide gel electrophoresis, followed by peroxidase staining. Then anthropometric or biochemical measurements were made: body composition, blood pressures, ventilatory responses, cholesterol (total, LDL cholesterol and HDL cholesterol), triglyceride, apolipoprotein A1, lipoprotein (a), creatine phosphokinase and lactate dehydrogenase. RESULTS: The gene frequencies of the Hp1-1, Hp2-1 and Hp2-2 phenotypes in Korean male athletes were 12, 37 and 51%, respectively; this polymorphism was significantly associated with the VO(2max) index in the athletes. An excess of the Hp1 allele was also observed in marathon runners compared with the other sporting activities, although it did not have any statistical significance. CONCLUSION: Hp polymorphism exists in elite Korean male athletes and Hp phenotype may be a useful marker for endurance performance in these male athletes.

Adult↗
PubMed2004

Role of haptoglobin phenotype in end-stage kidney disease.

BACKGROUND: We recently reported that haptoglobin (Hp) phenotype 1-1 is protective against the development of nephropathy in normal creatinine diabetics. In the present study, we sought to determine if Hp phenotype also plays a role in renal deterioration by determining Hp phenotypes in a consecutive series of patients with chronic renal failure (CRF) in hemodialysis (HD) and predialysis clinics. METHODS: Three hundred and ninety-two patients on HD for less than 2 years and 182 predialysis patients (creatinine clearance time [CCT] <35 ml/min) were subjected to Hp phenotyping. Age, gender and presence of diabetes or hypertension were recorded. Patients were stratified according to age (above and below 60 years) and severity of renal dysfunction (CRF or HD). RESULTS: We observed a markedly lower prevalence of the Hp 1-1 phenotype in HD patients under 60 years of age compared to patients with CRF or compared to the general population. This was not due to differences in the threshold for dialysis initiation among patients with different Hp types or to decreased survival of patients with Hp 1-1 prior to entering HD. In HD patients 60 years and over, Hp 1-1 prevalence was increased, as observed with other diseases in this age group. CONCLUSIONS: The prevalence of Hp 1-1 is decreased in HD patients less than 60 years of age. This may be due to a fundamental difference in the rate of renal deterioration in patients with different Hp types. In addition, Hp 1-1 may provide a protective effect against mortality in elderly patients.

Adult↗
PubMed1979

Possible linkage between alpha-haptoglobin (Hp) and depression spectrum disease.

Depression spectrum disease is an unipolar depressive illness in which at least one member of the family has unipolar depression and at least one other first degree relative has alcoholism and/or antisocial personality; using this definition, 14 depression spectrum disease families are studied. Assuming, among other things, that variability in age of onset is environmentally caused and lognormally distributed, segregation analysis shows that the data are compatible with the dichotomy of 'affected' versus 'not affected' being due to an autosomal dominant gene. A simple environmental hypothesis in which the transmission of the illness does not depend upon the parents' type could be rejected (p less than 0.001). Linkage analysis is performed by the method of maximum likelihood, taking the best fitting Mendelian model found in the segregation analysis. The results show virtually no evidence of linkage between depression spectrum disease and C3, but suggestive evidence (lod score = 1.03) of linkage between depression spectrum disease and alpha-haptoglobin (both these linkages were previously suggested by significant results in sib-pair analyses).

Adolescent↗