Hemopexin (HPX) is a plasma protein with the strongest binding capacity to heme and widely involved in modulation of a variety of physiological and pathological processes. The main physiological function of HPX is to bind and transport free toxic heme. Recent studies indicate that HPX also plays roles of anti-oxidant, anti-apoptosis, immune regulation and organic protection. In addition, HPX participates in regulation of cell differentiation and extracellular matrix reconstruction. In recent years, a great deal of progress has been made in studies of the mechanisms of HPX protective effects and on possible clinical application. In the past few years, especially, a number of proteomic studies have demonstrated that HPX could be served as positive molecular biomarkers for cancers of lung, liver, kidney, colon, and uterine myoma as well as osteoarthritis. In this review, recent progress in the biochemical characteristics and function of HPX and its possible clinical applications are summarized.
Heme ; Heme Oxygenase (Decyclizing) ; Hemopexin ; chemistry ; metabolism ; Humans

Heme oxygenase (HO)-1 is an inducible enzyme that catalyzes the first and rate-limiting step in the oxidative degradation of free heme into ferrous iron, carbon monoxide (CO), and biliverdin (BV), the latter being subsequently converted into bilirubin (BR). HO-1, once expressed during inflammation, forms high concentrations of its enzymatic by-products that can influence various biological events, and this expression is proven to be associated with the resolution of inflammation. The degradation of heme by HO-1 itself, the signaling actions of CO, the antioxidant properties of BV/BR, and the sequestration of ferrous iron by ferritin all concertedly contribute to the anti-inflammatory effects of HO-1. This review focuses on the anti-inflammatory mechanisms of HO-1 actions and its roles in inflammatory diseases.
Bilirubin ; Biliverdine ; Carbon Monoxide ; Ferritins ; Heme ; Heme Oxygenase (Decyclizing) ; Heme Oxygenase-1 ; Inflammation ; Iron

Heme oxygenase (HO)-1 is an inducible enzyme that catalyzes the first and rate-limiting step in the oxidative degradation of free heme into ferrous iron, carbon monoxide (CO), and biliverdin (BV), the latter being subsequently converted into bilirubin (BR). HO-1, once expressed during inflammation, forms high concentrations of its enzymatic by-products that can influence various biological events, and this expression is proven to be associated with the resolution of inflammation. The degradation of heme by HO-1 itself, the signaling actions of CO, the antioxidant properties of BV/BR, and the sequestration of ferrous iron by ferritin all concertedly contribute to the anti-inflammatory effects of HO-1. This review focuses on the anti-inflammatory mechanisms of HO-1 actions and its roles in inflammatory diseases.
Bilirubin ; Biliverdine ; Carbon Monoxide ; Ferritins ; Heme ; Heme Oxygenase (Decyclizing) ; Heme Oxygenase-1 ; Inflammation ; Iron

PURPOSE: The inducible isoform of heme oxygenase(HO), HO-1, responds to hypoxia. HO-1 regulates vascular smooth muscle tone through carbon monoxide production. To investigate the possible role of HO-1 in low-flow priapism, we examined the expression and activity of HO-1 in artificially induced veno-occlusive priapism in rat. MATERIALS AND METHODS: Fourteen male Sprague Dawley rats were divided into 2 groups with 7 rats each. In the first group, low-flow priapism was induced using a vacuum-constriction device and a constriction rubber band; in the second group, low-flow priapism was induced using papaverine. We measured the expression level and activity of HO-1 in penile tissues after time periods of 0(control), 2, 3, 4, 8, 12, 24, and 48 hours. At the same time, the expression levels of i-NOS, e-NOS, and beta-actin(control) in penile tissues were also measured. RESULTS: In both groups, expression of HO-1 and HO-1 enzyme activities in penile tissue significantly increased in a time dependent fashion(p<0.01). However, there was no difference in the expression of i-NOS and e-NOS in both groups at any time period. CONCLUSIONS: HO-1 was induced over time in rats with artificially induced veno-occlusive priapism. Induction of HO-1 may play a protective role against hypoxic injury, but may also play an important role in the vicious cycle observed for low flow priapism. Increasing induction of HO-1 against hypoxic injury in a prolonged erectile state promotes sustained dilatation of corporal smooth muscle, and this may aggravate low-flow priapism.
Animals ; Anoxia ; Carbon Monoxide ; Constriction ; Dilatation ; Heme Oxygenase (Decyclizing) ; Heme Oxygenase-1* ; Heme* ; Humans ; Male ; Muscle, Smooth ; Muscle, Smooth, Vascular ; Papaverine ; Priapism* ; Rats* ; Rats, Sprague-Dawley ; Rubber

The Porphyria are a group of inherited and acquired disorders characterized by partial defects in the heme biosynthetic pathway. Among the hepatic forms, acute intermittent porphyria(AIP) is the most severe and common type in western hemisphere. Though its association with pregnancy is rare, it presents the obstetrician with challenging problems in diagnosis and management and it is probable that pregnancy had some deleterious effect in acute porphyria. The authors present a cae of AIP in pregnancy with a review of literature.
Biosynthetic Pathways ; Diagnosis ; Heme ; Porphyria, Acute Intermittent* ; Porphyrias ; Pregnancy*

Carcinogenesis ; Cell Transformation, Neoplastic ; Heme Oxygenase-1 ; Humans

Catalases are well studied enzymes that play critical roles in protecting cells against the toxic effects of hydrogen peroxide. The ubiquity of the enzyme and the availability of substrates made heme catalases the focus of many biochemical and molecular biology studies over 100 years. In human, this has been implicated in various physiological and pathological conditions. Advancement in proteomics revealed many of novel and previously unknown features of this mysterious enzyme, but some functional aspects are yet to be explained. Along with discussion on future research area, this mini-review compile the information available on the structure, function and mechanism of action of human catalase.
Catalase ; chemistry ; metabolism ; physiology ; Heme ; chemistry ; Humans ; Hydrogen Peroxide ; metabolism

PURPOSE: To evaluate the neuroprotective effects of betaxolol (betaxolol hydrochloride) under hypoxic conditions using retinal ganglion cells (RGC-5) and determine whether heme oxygenase-1 (HO-1) expression exerts cytoprotective effects. METHODS: In this study, cultured RGC-5 cells were incubated with different concentrations of betaxolol hydrochloride (0.1 microM, 1 microM or 5 microM) and with 10 microM zinc protoporphyrin (ZnPP), in a hypoxia incubator (1% O2, 5% CO2, 94% N2) for 48 hours and the cell viability of each group was determined. Additionally, cell viability was measured after RGC-5 cells were incubated with 5 microM of brinzolamide (Azopt(R)), brimonidine tartrate (Alphagan(R)) or travoprost (Travatan(R)). RGC-5 cells were divided into three groups and incubated under three different conditions, normoxia group (20% O2, 5% CO2), hypoxia group (1% O2, 5% CO2) and the group with 5 microM of Betoptic S(R) treated under hypoxic conditions (hypoxia, Betoptic S(R)). After incubation for 4, 8, 12 and 24 hours, HO-1 expression was analyzed using Western blotting. RESULTS: Cell viability significantly increased in RGC-5 cells treated with Betoptic S(R) compared with other antiglaucoma agents. Increased levels of HO-1 expression indicate its relevance in cell viability. Furthermore, increased RGC-5 cell viability by Betoptic S(R) was significantly reduced in the HO-1 inhibitor ZnPP-treated group. CONCLUSIONS: We reaffirmed the known cytoprotective effects of Betoptic S(R) and the results suggests that HO-1 expression exerts cytoprotective effects against hypoxia.
Anoxia ; Betaxolol* ; Blotting, Western ; Cell Survival ; Heme Oxygenase-1* ; Heme* ; Incubators ; Neuroprotective Agents* ; Retinal Ganglion Cells ; Zinc ; Brimonidine Tartrate ; Travoprost

BACKGROUND: The overall response (20-30%) to chemotherapy in non-small cell lung cancer (NSCLC) is quite poor. Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in heme degradation. There is increasing evidence suggesting that the induction of HO-1 might have an important protective effect against oxidative stress including cisplatin containing chemotherapy. This study retrospectively investigated the relationship between HO-1 expression and the response to chemotherapy containing cisplatinin advanced NSCLC patients. MATERIAL AND METHODS: The medical records including the responses to chemotherapy of fifty nine cases were evaluated retrospectively, and the tissue samples of these patients were immunohistochemically stained for HO-1. RESULTS: Forty three of the fifty nine patients(72.8%) showed positive staining for HO-1 in their cancer tissues. There was no significant difference according to the cell type, stage and tumor size. In addition, there was no correlation between HO-1 expression and the responses to chemotherapy. CONCLUSION: HO-1 expression in tumor tissue dose not predict the response to cisplatin containing chemotherapy in advanced NSCLC. Further prospective studies with a larger number of patients will be needed to confirm these results.
Carcinoma, Non-Small-Cell Lung* ; Cisplatin* ; Drug Therapy* ; Heme Oxygenase-1* ; Heme* ; Humans ; Medical Records ; Oxidative Stress ; Retrospective Studies

The purpose of this study was to investigate effects of combined treatment with high intensity exercise and (-) epigallocatechin-3 gallate (EGCG), a potent free radical scavenger on a transcriptional level of hemoxygenase-1 gene in the large intestine. Sprague-Dawley rats were randomly divided into control group (CON, n=7), high intensity exercise group (HIE, n=7), EGCG group (EGCG, n=7), and EGCG plus high intensity exercise group (HIE + EGCG, n=7). Animals were given an intraperitoneal injection of EGCG with 50 mg of dosage per kg for four weeks 30 minutes before exercise. In order to induce HIE animals were allowed to ran on a treadmill with 0 degree of slope at speed of 28 m/min for 30 minutes. The exercise was performed four times a week for four week. The results of this study were as following; The expression level of hemoxygenase-1 mRNA of the high intensity exercise group was 15.21 times higher than that of the control group. The EGCG plus high intensity exercise group showed 5.98 times increased expression level of hemoxygenase-1 mRNA than control group. These results suggest that treatment of EGCG decrease the expression level of HO-1 mRNA through the removal of oxygen radicals produced by a high intensity exercise.
Animals ; Catechin ; Heme ; Heme Oxygenase-1 ; Injections, Intraperitoneal ; Intestine, Large ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; RNA, Messenger ; Tea