Disease relevance of HPR

• A circulating ligand for galectin-3 is a haptoglobin-related glycoprotein elevated in individuals with colon cancer [1].
• We have thus shown for the first time that the Hpr gene is expressed in the human hepatoma G2 and leukemia molt-4 cell lines [2].
• In patients with acute myocardial infarction, the haptoglobin (HP) groups were found to be associated with serum cholesterol levels [3].
• An analysis of haptoglobin (HP) phenotypes in 81 cases of diabetes mellitus (DM) without retinopathy and 122 cases with diabetic retinopathy (DR) were studied in relation to 180 normal and healthy controls matched for age and sex [4].
• Fenretinide [N-(4-hydroxyphenyl)retinamide; HPR] is a synthetic retinoid with minimal toxicity and favorable pharmacokinetics during long-term administration to patients in clinical trials [5].

Psychiatry related information on HPR

• In the brains of 21 patients with Alzheimer's disease (AD) and 10 nondemented controls, senile plaques (SPs), neurofibrillary tangles (NFTs), and three indexes of cholinergic function were quantified in the middle frontal (MF) and superior temporal (ST) cortex, the entorhinal cortex (HEN), and the prosubiculum (HPR) of the hippocampus [6].
• Repeated epileptic seizures and electroconvulsive therapy treatments produce successively less marked rises in serum HPR [7].

High impact information on HPR

• Haptoglobin-related protein (Hpr) epitopes in breast cancer as a predictor of recurrence of the disease [8].
• In NCI-H82 cells, HPR inhibited growth via the induction of apoptosis [5].
• In all cell lines tested, HPR was a more potent growth inhibitor than RA [5].
• Flow cytometric analysis revealed decreased DNA content, and TUNEL assay showed increased digoxigenin-uridine triphosphate incorporation in HPR-treated NCI-H82 SCLC cells; these findings are consistent with the induction of apoptosis [5].
• METHODS: Seven SCLC cell lines (NCI-H69, NCI-H82, NCI-H146, NCI-H209, NCI-H345, NCI-H446, and NCI-H510A) were exposed continuously to a broad range of concentrations of HPR or all-trans-retinoic acid (RA), and cell viability was determined on day 3 and day 7 by the trypan blue dye exclusion assay [5].

Chemical compound and disease context of HPR

• A study on plasma concentrations of HPR, of its metabolite N-(4-methoxyphenyl)retinamide (MPR), and on its effects on endogenous retinol was performed in groups of 14 to 18 breast cancer patients who received p.o. daily doses of placebo or 100, 200, and 300 mg of HPR for 6 mo and subsequently 200 mg for an additional 6 mo [9].
• Previously, we reported that the synthetic retinoid N-(4-hydroxyphenyl)retinamide (fenretinide, HPR) induces apoptosis in neuroblastoma cells, sharing a neuroectodermal origin with melanoma cells [10].
• According to cytofluorimetric analysis, propidium iodide staining and TUNEL assay, HPR-treated melanoma cells were shown to undergo apoptosis [10].
• Because of the normal diurnal variation in serum cortisol levels and the relative delay in the postictal elevation of serum cortisol, HPR is more useful as a diagnostic measure of epileptic seizures [7].
• An easy, rapid, and accurate enzymatic assay method for L-serine was established involving two enzymes, serine-glyoxylate aminotransferase (SGAT, EC 2.6.1.45) and hydroxypyruvate reductase (HPR, EC 1.1.1.81), in the serine pathway of the methylotrophic bacterium, Hyphomicrobium methylovorum (IFO 14180), from which they were purified [11].

Biological context of HPR

• Transient expression in HepG2 cells of plasmids carrying the HPR promoter joined by a shortened version of intron 1 to the chloramphenicol acetyltransferase (CAT) vector showed that fragments containing the 5' long terminal repeat (LTR) had no significant effect [12].
• Similar to in vitro experiment, insertion of this fragment into an HPR transgene in mice reduced HPR expression to 50% compared to a transgene without the insert, but none of the viral sequence motifs appear to explain this effect [12].
• His other chromosome had one Hpr gene [13].
• We have found polymorphisms for the number of tandemly arranged haptoglobin-related (Hpr) genes in the haptoglobin gene cluster of Blacks [13].
• An intronic endogenous retrovirus-like sequence attenuates human haptoglobin-related gene expression in an orientation-dependent manner [12].

Anatomical context of HPR

• DNA analysis of the hybrid cells showed that in both individuals the tandemly arranged Hpr genes are linked to the Hp2 allele [13].
• Purified human Hpr and human Hp bind to trypanosomes, are internalized, and are targeted to the lysosome [14].
• We explored the effectiveness of 4-oxo-4-HPR in inducing cell growth inhibition in ovarian, breast, and neuroblastoma tumor cell lines; moreover, we investigated the molecular events mediating this effect in two ovarian carcinoma cell lines, one sensitive (A2780) and one resistant (A2780/HPR) to 4-HPR [15].
• These data suggest that HPR exerts its antiangiogenic activity through both a direct effect on endothelial cell proliferative activity and an inhibitory effect on the responsivity of the endothelial cells to the proliferative stimuli mediated by angiogenic growth factors [16].
• Counts were made of SPs and NFTs on the left and right side of five different brain areas, which included middle frontal, superior temporal, the prosubiculum of the hippocampus (HPR), the entorhinal cortex of the hippocampus (HEN), and the basal nucleus of Meynert [17].

Associations of HPR with chemical compounds

• A second copy of the retrovirus-like sequence occurs between Hpr and Hpp [18].
• After the duplication event, the first intron of the Hpr gene acquired a 9-kb insert consisting mainly of a retrovirus-like element with a potential primer-binding site homologous to a mouse isoleucine tRNA [19].
• Haptoglobin and haptoglobin-related protein are homologous hemoglobin-binding proteins consisting of a complement control repeat (alpha-chain) and a serine protease domain (beta-chain) [20].
• Transcription/translation assay was used to demonstrate that the Hpr message could be translated from the internal methionine codon [2].
• Fenretinide (HPR) is a synthetic retinoid which has been shown to cause a reduction in the incidence of carcinogen-induced epithelial tumors in experimental animals, and it has been chosen to be tested as a chemopreventive agent in humans [9].

Physical interactions of HPR

• 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 [14].
• However, in contrast to Hp, Hpr did not promote any high-affinity binding to the scavenger receptor CD163 [21].

Regulatory relationships of HPR

• Oncogenic antigen 519 (OA-519) is the new marker designation for molecules expressing haptoglobin-related protein epitopes [22].

Other interactions of HPR

• The immunohistochemical reactivity of antibodies raised to the synthetic Hpr peptide is similar to that of anti-PAPP-A [23].
• Twenty percent of these genes were previously known to be tumor related and those most frequently appearing were haptoglobin alpha(2FS)-beta precursor, haptoglobin related protein, and alpha-2-macroglobulin [24].
• In A2780/HPR cells continuously treated with 4-HPR and producing 4-oxo-4-HPR, CYP26A1 and CRBP-I were markedly up-regulated compared with A2780 untreated cells [25].
• Pathological causes for HPR secretion include destructive lesions of the hypothalamus, prolactin-secreting neoplasms of the pituitary gland, lesions of the spinal cord, and occasionally Parkinson's disease [7].
• The postictal elevation of serum cortisol has a longer latency than for HPR and follows an earlier rise in serum ACTH [7].

Analytical, diagnostic and therapeutic context of HPR

• 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) [26].
• A simple isoelectric focusing method for haptoglobin (HP) typing is described [27].
• The synthetic retinoid fenretinide (HPR) inhibits carcinogenesis in various animal models [16].
• Results showed that HPR perimetry is more suitable to children [28].
• We retrospectively examined the association between the expression of Hpr and the recurrence of cancer in 70 patients with early breast cancer (Stage I or II) treated by mastectomy from 1977 through 1985, using immunohistochemical analysis of routinely processed paraffin-embedded tissue and evaluating it without knowledge of the patients' status [8].

References