Disease relevance of Hp

• Immunohistochemistry for haptoglobin (Hp) in the postischemic hippocampus demonstrated an immunoreactivity visible one day after reperfusion and continuing to increase until 14 days after ischemia [1].
• These findings suggest that Hp is synthesized in reactive astrocytes in response to ischemia-reperfusion injury [1].
• The Hp gene expression was also upregulated in C6 and A-172 glioblastoma cell lines after H O treatment [1].
• Hepatic expression of the haptoglobin (Hp) gene in mammalian species is stimulated severalfold during an acute-phase reaction [2].
• The regulatory elements of the rat Hp gene were similarly active in human hepatoma cells [3].

High impact information on Hp

• Twelve and five bands were resolved in the haptoglobin and postalbumin regions, respectively, when sera from pyridoxine-depleted tumor-bearing rats were electrophoresed [4].
• Proteolytic cleavage of haptoglobin occurs in a subcompartment of the endoplasmic reticulum: evidence from membrane fusion in vitro [5].
• The effect of reduced cellular ATP content on intracellular transport of two secretory proteins, albumin and haptoglobin, in isolated rat hepatocytes was studied [6].
• By similar criteria it was found that at ATP levels below 10% of normal transport of haptoglobin from the endoplasmic reticulum to the medial GC (and possibly also to the cis GC) as well as from the trans GC to the medium were blocked [6].
• At these FDP concentrations the synthesis of albumin, haptoglobin, and transferrin was not increased [7].

Chemical compound and disease context of Hp

• Similarly, CNTFR3alpha specifically antagonizes the induction of gp130 and LIFRbeta tyrosine phosphorylation observed in response to CNTF and wild type soluble CNTFRalpha in the HepG2 hepatoma cell line, as well as the subsequent events leading to haptoglobin synthesis [8].
• The concentration of free hemoglobin and the binding capacity of haptoglobin in plasma, both indicators of in vivo hemolysis, did not differ between rats fed the salmon oil diet with 100 or 10,000 mg TA/kg [9].
• Changes associated with tissue injury were assessed by neutropenia, intestinal edema, serum tumor necrosis factor-alpha, serum haptoglobin, plasma aspartate aminotransferase, and histopathology [10].
• Feeding of ursodeoxycholic and iso-ursodeoxycholic acid markedly down-regulated alpha2-macroglobulin and TIMP-1 expression in cholestasis but did not affect overexpression of beta-fibrinogen and haptoglobin [11].
• It was found that hepatoma synthesizes fibrinogen, alpha 1-AP-globulin and alpha 1-acid glycoprotein in the amounts comparable to rat liver, whereas formation of albumin and haptoglobin is reduced 5- to 10-fold [12].

Biological context of Hp

• Previously observed acute phase-dependent elevation of Hp gene transcriptional activity in prenatal liver was accompanied by increased binding affinities of several fetal soluble nucleoproteins and the hormone response element (RE) of the Hp gene (-170/-56) [13].
• The rat beta-subunit shows a high degree (approximately 80%) of sequence homology with its human counterpart although it possesses only two of the four N-glycosylation sites present in human haptoglobin beta-subunit [14].
• Nucleotide sequence of rat haptoglobin cDNA. Characterization of the alpha beta-subunit junction region of prohaptoglobin [14].
• Upregulation of haptoglobin in reactive astrocytes after transient forebrain ischemia in rats [1].
• p53-like protein binding affinity to the hormone responsive element of the haptoglobin gene in fetal rat livers [13].

Anatomical context of Hp

• Furthermore, a reverse transcription-polymerase chain reaction study confirmed an elevated Hp mRNA level in the postischemic hippocampus [1].
• Growth stimulation of hepatic cells in vivo or in vitro suppresses the Hp gene-inducing effects of inflammatory cytokines [15].
• Using a 351-bp cDNA coding for Hp for northerns and two Hp primers for RT-PCR, we have demonstrated the expression of Hp in Sertoli and Leydig cells, germ cells, and the testis, but not in the epididymis [16].
• Parenchymal cells, but not Kupffer cells, in the liver were stained with anti-Hb or anti-Hp IgG after administration of Hb in an amount corresponding to the Hb binding capacity of Hp [17].
• Among these proteins, haptoglobin (Hp) which is related to inhibition of T-cell proliferation was found to be up-regulated following OLT [18].

Associations of Hp with chemical compounds

• Structure, hormonal regulation, and identification of the interleukin-6- and dexamethasone-responsive element of the rat haptoglobin gene [2].
• 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 [3].
• The half-cystine residue at position 15 in the L chain, which participates in the inter-L chain disulfide bridging in human Hp, has been replaced by a leucine residue in canine Hp [19].
• The plasma protein synthetic capacity and the in vitro response to insulin plus cortisol of perfused livers from insulin-treated diabetic rats were normal for seven of the proteins but moderately decreased for albumin, haptoglobin and C3 [20].
• Chronic liver damage induced by thioacetamide (TAM) was accompanied by changes in the expression of genes related to growth (beta-actin) and function (albumin and haptoglobin) of the liver [21].

Physical interactions of Hp

• By DNA binding assays we found the HMG-1 binding sites in the rat Hp gene cis-regulatory subelements A and C and revealed an increase in its DNA-binding after induction of AP response [22].

Regulatory relationships of Hp

• HMG-1 as regulatory trans-acting protein in the acute phase-induced expression of the rat liver haptoglobin gene [22].

Other interactions of Hp

• Double immunofluorescence histochemistry confirmed colocalization of the Hp and glial fibrillary acidic protein [1].
• The results presented in this report offered further evidence for the existence of structural and functional similarities between these two proteins implicating an involvement of HMG-1 in the regulation of the rat Hp gene transcription [22].
• In this study AO (Albino Oxford) and DA (Dark Augustin) inbred strains of rats, with different resistance to trauma, were used to compare concentrations of Hp, alpha 2-M, IL-1, IL-6 and TNF, before and after tourniquet trauma [23].
• Furthermore, p42/p44 MAP kinases may function in a TGFbeta-dependent signaling pathway leading to attenuation of haptoglobin expression [24].
• The IL-1-dependent induction of the acute phase protein gene haptoglobin in IEC-6 cells was decreased in response to the p38 MAP kinase inhibitor SB203580, as determined by Northern blot [25].

Analytical, diagnostic and therapeutic context of Hp

• Comparative sequence analysis of the N-terminal region of rat, rabbit, and dog haptoglobin beta-chains [26].
• Western blot analyses using anti-Hp antibody demonstrated cross-reactivity with de novo-synthesized ENDO-I protein in endometriosis culture media [27].
• In conclusion, the presence of Hp may play an important role in modulating the spontaneous tolerance of liver transplantation [18].
• Hp also exhibited a strong in vitro immunosuppressive effect on the mixed lymphocyte reaction [18].
• Direct protein sequence analysis of the 9-kDa subunit revealed a sequence of NH2-VELGNDATDIEXD, which is identical to the alpha subunit of the rat haptoglobin (Hp) [16].

References