Disease relevance of Hpxn

• Defective recovery and severe renal damage after acute hemolysis in hemopexin-deficient mice [1].
• After hemolytic stimulus, Hx-deficient mice presented prolonged hemoglobinuria with a higher kidney iron load and higher lipid peroxidation than control mice [1].
• Enhanced splenomegaly and severe liver inflammation in haptoglobin/hemopexin double-null mice after acute hemolysis [2].
• Results of binding studies using mouse hepatoma cells and isolated domains indicate that domain I not only binds heme but also plays a vital part in the hemopexin-receptor interaction [3].
• In this study we have made chimeric constructs combining promoter and enhancer regions of the albumin, alpha 1-antitrypsin, hepatitis B virus core protein, and hemopexin genes [4].

High impact information on Hpxn

• Analysis of single-null mice demonstrated the antioxidant action of haptoglobin and hemopexin in vivo and suggests that the 2 proteins cooperate in the resolution of hemolytic stress [2].
• Hemopexin (Hx) is a plasma glycoprotein mainly expressed in liver and, less abundantly, in the central and peripheral nervous systems [1].
• These data indicate that, although Hx is not crucial either for iron metabolism or as a protection against oxidative stress under physiologic conditions, it does play an important protective role after hemolytic processes [1].
• These data demonstrate for the first time that the hemopexin domain of MMP-9 has a high affinity binding site for gelatin, and the particular recombinant domain is able to block MMP-9 activity and tumor cell invasion [5].
• The structure of the exons encoding the catalytic domain and pro-domain of MMP-14 is distinct from previously described MMP genes, whereas the exons encoding the hemopexin-like domains are similar to those of most other MMP genes [6].

Biological context of Hpxn

• Whereas haptoglobin-hemopexin double-null mice displayed no obvious alteration in phenotype under basal conditions, nonlethal hemolytic stress in these animals led to pronounced splenomegaly as well as liver inflammation and fibrosis [2].
• Transgenic mice harboring the human hemopexin promoter sequences linked to the lacZ reporter gene were generated and analyzed for temporal and spatial distribution of beta-galactosidase [7].
• Deletion and mutation analyses of the MT-1 proximal promoter revealed that the sequence 5'-GTGACTATGC-3' (from -98 to -89 base pairs) is, in part, responsible for the hemopexin-mediated regulation of MT-1 which is inhibited by H7 [8].

Anatomical context of Hpxn

• Among plasma-protective proteins against oxidative damage caused by red blood cell rupture, haptoglobin and hemopexin are thought to play a crucial role [2].
• Hepatocytes on matrigel secreted substantially higher amounts of albumin, transferrin, haptoglobin, and hemopexin, Northern blot analyses of extracted cellular RNA, expressed increased amounts of mRNA for the liver-specific protein albumin (as compared with cells on vitrogen) [9].
• Respective roles of inflammation and axonal breakdown in the regulation of peripheral nerve hemopexin: an analysis in rats and in C57BL/Wlds mice [10].
• We also show that HPX synthesis is dramatically increased in macrophages during their activation or after IL-6 stimulation [10].
• We conclude that, after nerve injury, HPX overexpression occurs first in Schwann cells as a result of axotomy and is subsequently regulated by inflammation [10].

Associations of Hpxn with chemical compounds

• A new bioactive factor capable of stimulating the production of acute-phase transport proteins, haptoglobin, hemopexin and ceruloplasmin, was found in mouse serum soon after the administration of lentinan, an immunomodulatory polysaccharide [11].
• The greatest changes (four-fold 48 h after LPS administration) were observed for haptoglobin and hemopexin [12].
• Consequently, the increases in haptoglobin and hemopexin were marked and 90% or more of the increased sialic acid was derived from these two glycoproteins after exposure to UV radiation [13].
• Biol. Chem. 259, 12049-12053) contains only 4 histidine residues which are conserved in rabbit, human, rat, and mouse hemopexin [14].
• This conformational change which plays a pivotal role in hemopexin function requires the bis-histidyl coordination with heme iron and leads to a tighter association between domain I and domain II shown by the co-migration of heme-domain I and domain II in sucrose gradients [3].

Other interactions of Hpxn

• Membrane phospholipid reorganization differentially regulates metallothionein and heme oxygenase by heme-hemopexin [15].
• Concentrations of hemopexin, a porphyrin-binding serum protein synthesized exclusively in the liver, increased significantly and concomitantly with levels of erythrocyte and liver protoporphyrin and coproporphyrin in mice made porphyric with 1% griseofulvin in the feed [16].

Analytical, diagnostic and therapeutic context of Hpxn

• By contrast, mRNA expression of another heme binding protein, hemopexin, was not induced in hepatocyte cell cultures by heme or heavy metals [17].
• Finally, a positive statistical correlation between solid type tumor weight and hemopexin concentration in the mouse was observed [18].

References