Disease relevance of Hpx

• Regulation of hemopexin transcription by calcium ionophores and phorbol ester in hepatoma cells [1].
• To induce acute liver failure, Lewis rats were subjected to 90% hepatectomy (Hpx) and given 5% oral dextrose [2].
• Body-weight gain, body-length gain and serum levels of rat insulin-like growth factor-I (rIGF-I) induced by subcutaneous injection of rhGH-SR were compared with those by daily injections of rhGH solution in Hpx rats for 35 days [3].
• Interaction of hemopexin, albumin and liver fatty acid-binding protein with protoporphyrin [4].
• In turn, these results support the idea that hemopexin could be involved in the process of Wallerian degeneration and/or in nerve repair [5].

High impact information on Hpx

• Albumin-producing SV40-immortalized hepatocytes secreted a variety of other plasma proteins, including transferrin, hemopexin, and the third component of complement [6].
• The protein sequence encoded by the last four exons of the transin gene shows some homology to two regions of the heme-binding protein hemopexin [7].
• These results suggest that heme, in amounts sufficient to affect the rate-limiting steps of heme synthesis and degradation, can only enter hepatocytes in primary culture when the binding capacity of hemopexin for heme has been exceeded or altered [8].
• A 44-kDa remnant of MT1-MMP, with an N terminus at Gly(285), is also present on the cell after autolytic shedding of the catalytic domain from the hemopexin carboxyl (C) domain, but its role in gelatinase A activation is unknown [9].
• With the exception of G-CSFR-MPL chimera, the receptors also mediated a similarly high stimulation via the IL-6 response element of the rat beta-fibrinogen and hemopexin genes [10].

Chemical compound and disease context of Hpx

• The transcription rate of Hx was found to be increased 11-fold by the calcium ionophore A23187, 25-fold by the calcium ionophore ionomycin, and 4-5-fold by phorbol 12-myristate 13-acetate (PMA) in serum-starved H4IIE rat hepatoma cells [1].
• A maximum acute-phase response on d 7 after the operation was characterized by an increase of 181, 445, and 19% for alpha-1-acid glycoprotein, hepatoglobin, and hemopexin, whereas other acute-phase proteins remained below control levels, for example, by 11, 25, and 38% for albumin, transferrin, and prealbumin, respectively [11].

Biological context of Hpx

• Rat hemopexin. Molecular cloning, primary structural characterization, and analysis of gene expression [12].
• A full-length hemopexin cDNA was isolated from a rat liver cDNA library and the derived amino acid sequence was obtained [12].
• The abundance of hemopexin mRNA was found to increase throughout gestation, with a sharp increase in the first postnatal weeks, reaching maximum levels in adult animals [12].
• The activities of putative regulatory regions joined to the SV40 promoter indicated that the flanking region of the rat Hx gene from -209 to -104 contains three functional regions designated proximal regulatory regions; PRR-I (-209 to -173), -II (-178 to -158) and -III (-154 to -104) [13].
• Identification of an interleukin-6 responsive element and characterization of the proximal promoter region of the rat hemopexin gene [13].

Anatomical context of Hpx

• Analysis of molecular components of tissue environments that allow axonal regrowth revealed a dramatic increase in the level of hemopexin, a heme-transporting protein, in long-term axotomized peripheral nerve [14].
• In contrast, hemopexin did not accumulate in lesioned optic nerve [14].
• Sciatic nerve and skeletal muscle, but not brain, were shown to be sites of synthesis of hemopexin [14].
• Hemopexin-specific mRNA was not detected in embryonic or fetal tissues at earlier stages of development and was confined to the liver throughout fetal, newborn, and adult life [12].
• Survival after intraperitoneal injection of a cellular homogenate of 200 x 10(6) primary Lewis rat (G7, n=9) or SV40ts-ci hepatocytes (G8, n=10) on the day of Hpx was 33% and 40%, respectively, whereas survival after intraperitoneal injection of 200 x 10(6) Lewis rat bone marrow cells (G6, n=7) was 29% [2].

Associations of Hpx with chemical compounds

• Adult animals exposed to hyperoxia (95% oxygen) showed a 3-fold increase in hepatic hemopexin mRNA content.(ABSTRACT TRUNCATED AT 250 WORDS)[12]
• The amino-terminal domain of rat hemopexin contains two histidine residues that are conserved in the human and rat sequences and are the most likely heme axial ligands [12].
• When hepatocytes were maintained in CDM supplemented with dimethyl sulfoxide and transfected with plasmids containing the E1A and E1B genes, it was possible to derive cell lines that retained the ability to express several liver-specific genes, including albumin, transferrin, hemopexin, and the third component of complement [15].
• To assess if the observed increase in Con-A reactivity of specific serum proteins reflects an increase in carbohydrate moieties in these proteins in addition to an increase in their protein concentrations, a heme binding serum glycoprotein, hemopexin, also an acute phase reactant, was selected as a marker protein [16].
• Abnormal glycosylation of hemopexin in arthritic rats can be blocked by bindarit [16].

Regulatory relationships of Hpx

• In growing cultures, the IL-6 and IL-11 stimulation of thiostatin and hemopexin is enhanced by TGF-beta, whereas the stimulation of other APP is reduced [17].

Other interactions of Hpx

• Serum IGF-I levels in Hpx rats after the injection of rhGH-SR2W microcapsules were higher than those after daily injections of rhGH solution [3].
• In injured peripheral nerves, hemopexin mRNA is expressed by fibroblasts, Schwann cells, and invading blood macrophages, and the protein accumulates in the extracellular matrix [18].
• Effects of leukocytic endogenous mediator on hemopexin, transferr, and liver catalase [19].
• Liver heavy-chain ferritin mRNA, hemopexin, ceruloplasmin and cellular retinol-binding protein mRNA were not affected by iron or VA restriction [20].
• By contrast, both the minor intracellular and the extracellular species of hemopexin were neuraminidase-, yet not endoglycosidase H-sensitive, and may be identical [21].

Analytical, diagnostic and therapeutic context of Hpx

• Hemopexin is synthesized in peripheral nerves but not in central nervous system and accumulates after axotomy [14].
• Using hemopexin cDNA probes (GIG-3, -7, and -12) we identified a mRNA on Northern blots, which increased in concentration following bGH, compared with untreated cells [22].
• It was found that the Hpx rats, given subcutaneous injections of GH twice during the light period to mimic a male pattern of GH secretion, showed obvious light-dark fluctuation in ACD activities with high values in the dark period, and similar results were obtained in sham-operated males [23].
• After hypophysectomy (Hpx) thyroid involution ensued [24].
• When a new liver was inserted into the perfusion medium containing newly synthesized secreted proteins, only two proteins, hemopexin and an unidentified protein, were transported into the bile from the perfusion medium; other biliary proteins were presumed to come directly from the hepatocyte [25].

References