Disease relevance of HEPH

• The iron exporter FPN was also overexpressed, but its intracellular location, combined with reduced HEPH levels, suggests reduced iron efflux in the majority of colorectal cancers examined [1].
• Mutations in the murine hephaestin gene (sla) produce microcytic, hypochromic anemia that is refractory to oral iron therapy [2].
• Using quantitative PCR, we measured mRNA expression of divalent cation transporter 1 (DCT1), iron-regulated gene 1 (IREG1), and hephaestin in duodenal biopsy samples of individuals with normal iron levels, iron-deficiency anemia, or iron overload [3].
• Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload and retinal degeneration with features of age-related macular degeneration [4].
• Among the factors considered in the postoperative classification, lymph node metastasis demonstrated high values in cervical infiltration cancer, positive parametrial infiltration, positive vaginal invasion, and infiltration into the uterine body and L type of CPL classification [5].

Psychiatry related information on HEPH

• In April, testes and CPL develop rapidly reaching a peak in early May when females are laying eggs, and when most copulations occur [6].

High impact information on HEPH

• We suggest that the hephaestin protein is a multicopper ferroxidase necessary for iron egress from intestinal enterocytes into the circulation and that it is an important link between copper and iron metabolism in mammals [7].
• Studies with HEPH reporter gene constructs and chromatin-immunoprecipitation approaches suggested that CDX2 directly regulates HEPH transcription [8].
• Duodenal cytochrome b and hephaestin expression in patients with iron deficiency and hemochromatosis [9].
• In normal mice, Cp and Heph localize to Müller glia and retinal pigment epithelium, a blood-brain barrier [4].
• The roles of proteins such as iron regulatory proteins, the hereditary hemochromatosis protein (HFE)-transferrin receptor complex, and hephaestin in regulating this transporter and in regulating iron transport across the intestinal epithelium are discussed [10].

Chemical compound and disease context of HEPH

• METHODS: Tissues were obtained from 22 pregnant ewes under halothane anesthesia: early controls at 131 days' gestational age (dGA) not in labor (ECNL; n = 6); during cortisol-induced premature labor (CPL at 131 dGA; n = 6); in term spontaneous labor (STL at 140-145 dGA; n = 5); or term control animals not in labor (TCNL at 140-145 dGA; n = 5) [11].

Biological context of HEPH

• Duodenal Dcytb and hephaestin mRNA expression are not significantly modulated by variations in body iron homeostasis [12].
• To test this hypothesis, human hephaestin cDNA has been cloned by reverse transcription of human duodenal mRNA [2].
• Following in vitro mutagenesis to make the encoded polypeptide suitable for expression and purification, the hephaestin cDNA was cloned into the expression vector pNUT and introduced into baby hamster kidney cells [2].
• Cell surface biotinylation and immunofluorescent studies of polarized, differentiated colon carcinoma cells detected hephaestin on the basolateral surface under steady-state conditions [13].
• Immunoblot analysis and pulse-chase metabolic labeling revealed that hephaestin is synthesized as a single-chain polypeptide modified by N-linked glycosylation to a mature 161-kDa species [13].

Anatomical context of HEPH

• SFT (Stimulator of Iron Transport) is postulated to facilitate both ferric and ferrous iron uptake, and Hephaestin is thought to be important in transfer of iron from enterocytes into the plasma [14].
• The expression and regulation of the iron transport molecules hephaestin and IREG1: implications for the control of iron export from the small intestine [15].
• Mice deficient in both Cp and Heph, but not each individually, had a striking, age-dependent increase in retinal pigment epithelium and retinal iron [4].
• RESULTS: We have demonstrated that hephaestin is primarily localised to a supranuclear compartment in both intestinal enterocytes and in cultured cells [16].
• Taken together, these studies demonstrate the presence of a quality control system for posttranslational protein modification occurring beyond the endoplasmic reticulum that, in the case of hephaestin, directly links the rate of enteric iron uptake to nutritional copper status [13].

Associations of HEPH with chemical compounds

• After selection with methotrexate, the baby hamster kidney cells secreted the recombinant human hephaestin into the medium at a level of approximately 2 mg/L [2].
• Lastly, urea PAGE showed that hephaestin was able to catalyze formation of diferric transferrin from Fe(II) and apotransferrin [2].
• By using ferrous ammonium sulfate as a substrate, recombinant hephaestin was shown to have ferroxidase activity with a K(m) of 2.1 microM for Fe(II) [2].
• The luminescence properties including CPL, of the three complexes and their sensitivity to dioxygen were examined [17].
• At pH 1, the op of Ala and Leu determined by circular dichroism (CD) spectral measurement gradually developed with CPL irradiation, according to Kagan's equation [18].

Physical interactions of HEPH

• On the basis of this similarity to ceruloplasmin, human hephaestin may also bind copper and possess ferroxidase activity [2].
• The basolateral transfer of iron requires two components: a copper-containing iron oxidase known as hephaestin and a membrane transport protein IREG1 [15].

Other interactions of HEPH

• Hephaestin and Dcytb levels were not upregulated in haemochromatosis [19].
• These results suggest that DMT1, Fpn1, and Heph are involved in the iron uptake process modulated by copper status [20].
• Our data show that expression levels of human DCT1 mRNA, and to a lesser extent IREG1 mRNA, are regulated in an iron-dependent manner, whereas mRNA of hephaestin is not affected [3].
• Recombinant expression and functional characterization of human hephaestin: a multicopper oxidase with ferroxidase activity [2].
• HFE expression did not affect the mRNA levels of most of the genes involved in iron absorption that were tested; however, it did correspond to a decrease in hephaestin message levels [21].

Analytical, diagnostic and therapeutic context of HEPH

• As judged by SDS-PAGE, N-terminal sequence analysis, and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry, the purified hephaestin was homogeneous with a mass of 129600 Da, suggesting a carbohydrate content of 7.7% [2].
• The histologic grade of regression of 50 osteosarcomas after polychemotherapy - according to the protocol study, COSS 80 - was classified on a six-stage regression scale; 56% of all patients responded well to chemotherapy regression grades I, II, and III and no significant difference between BCD- and CPL-treated patients could be found [22].
• Recognizing that the patients who comprise the conditionally released CPL 330 category are heterogeneous and multiply disabled, techniques for active focused rehabilitation treatment will be explored [23].

References