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

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

OBJECTIVETo investigate the location of heme oxygenase (HO) enzyme in the human testis, and explore the correlation of the expression of HO enzyme with azoospermia by analyzing its different expression levels in the testes of nonobstructive azoospermia, obstructive azoospermia and normal men.

METHODSWe detected the location of the cells expressing HO enzyme in the human testis tissue using immunohistochemistry, determined the mRNA and protein expression levels of HO-1 and HO-2 in the testes of azoospermia patients and normal healthy men by RT-fluorescence quantitative PCR (RT-FQ-PCR) and Western blot, and explored the correlation of HO expressions with the pathogenesis of azoospermia.

RESULTSHO-1 enzyme was expressed mainly in the Sertoli cells and HO-2 enzyme chiefly in the germ cells of the testis tissue. RT-FQ-PCR showed that the expression of HO-1 in the testis tissue was significantly lower in the nonobstructive azoospermia than in the normal and obstructive azoospermia groups (P < 0.05), with no significant difference between the latter two. Western blot revealed no obvious difference between the expression level of HO-1 protein and that of HO-1 mRNA. There were no differences in the expression level of HO-2 protein among the three groups.

CONCLUSIONThe expression level of HO enzyme is significantly decreased in the testis tissue of nonobstructive azoospermia patients, and the expression of HO-1 protein is consistent with that of HO-1 mRNA. As HO-1 protects the testis tissue against various stress injuries through its antioxidant, anti-inflammatory and anti-apoptotic effects, its decreased expression level may be correlated with spermatogenic dysfunction, and therefore considered as a possible mechanism of nonobstructive azoospermia.

Azoospermia ; enzymology ; metabolism ; Case-Control Studies ; Heme Oxygenase (Decyclizing) ; metabolism ; Heme Oxygenase-1 ; metabolism ; Humans ; Male ; Spermatogenesis ; Testis ; enzymology ; metabolism

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

To explore the expression of heme oxygenase-1 (HO-1) in the peripheral blood mononuclear cells (PBMCs) and its relationship with pulmonary ventilation function in asthmatic patients, 18 asthmatic patients and 18 healthy subjects were selected. HO-1 protein and mRNA levels in PBMCs were measured by immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Blood carbon monoxide Hb (COHb), serum total IgE and pulmonary ventilatory function were observed. Our results showed that the percentage of cells positive for immunohistochemical staining of HO-1 were significantly higher in asthmatic patients (41.72 +/- 7.44) % than that in with healthy subjects (10.45 +/- 4.36) % (P < 0.001) and the optical density of PBMC HO-1 mRNA was higher in asthmatic patients (26.05 +/- 4.14) than that in healthy subjects (10. 82 +/- 4.26) (P < 0.001). The relation analysis showed that PBMC HO-1 protein and mRNA levels had significantly negative relation with FEV1%, PEFR, MEFR50%, respectively (r = -0.51-0.89, P < 0.05-0.001, respectively) and a positive relation with COHb and serum total IgE (r = 0.48-0. 85, 0.05-0.001, respectively). It is concluded that the expression of PBMC HO-1 protein and mRNA increased significantly in asthmatic patients, and HO-1 may play a significant role in the pathogenesis of asthma. The expression of HO-1 may bear a relation with severity of asthma.
Asthma/blood ; Asthma/*enzymology ; Carbon Monoxide/blood ; Heme Oxygenase-1/*biosynthesis ; Heme Oxygenase-1/blood ; Immunoglobulin E/*blood ; Leukocytes, Mononuclear/*enzymology ; RNA, Messenger/blood

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

PURPOSE: To evaluate the effects of oxidative stress and antioxidantson heme oxygenase-1 (HO-1) in cultured human retinal pigment epithelial (RPE) cells. METHODS: Cultured RPE cells were challenged with different concentrations of hydrogen peroxide (H2O2), and the HO-1 mRNA level was determined by RT-PCR after 24 hours and 48 hours of incubation independently. Additionally, the HO-1 mRNA level was measured after preincubating RPE cells with N-acetylcystein (NAC) as the antioxidant for 30 minutes and then challenging the cells with H2O2. RESULTS: The expression of the HO-1 mRNA level increased after H2O2 exposure, and this level was proportional to the increased H2O2 concentration (p<0.05). Expression of the HO-1 mRNA level decreased when the RPE cells were preincubated with NAC (p<0.05). CONCLUSIONS: In human RPE cells, the HO-1 level increased in proportion to the degree of oxidative stress and decreased with exposure to antioxidants. Expression of HO-1 may be helpful in preventing retinal disease, which occurs due to oxidative stresses such as age-related macular degeneration.
Antioxidants ; Heme ; Heme Oxygenase-1 ; Humans ; Hydrogen Peroxide ; Macular Degeneration ; Oxidative Stress ; Retinal Diseases ; Retinal Pigment Epithelium ; Retinaldehyde ; RNA, Messenger