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

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

In order to investigate the relationship between the expression of heme oxygenase-2 (HO-2) mRNA and the pathogenesis of Hirschsprung's disease (HD), total ribonucleic acid (RNA) was extracted in the aganglionic and ganglionic segments of colon respectively from 15 cases of HD. The single-stranded cDNA of HO-2 was synthesized and further amplified by reverse transcription-polymerase chain reaction (RT-PCR). The expression of HO-2 mRNA was normal in ganglionic segments, but absent in aganglionic segments. It is concluded that the absence of HO-2 mRNA expression may be an important mechanism responsible for HD.
Colon/enzymology ; Heme Oxygenase (Decyclizing)/biosynthesis ; Heme Oxygenase (Decyclizing)/*genetics ; Hirschsprung Disease/*enzymology ; Hirschsprung Disease/etiology ; Hirschsprung Disease/genetics ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics

This study investigated the expression of hemeoxygenase-1 (HO-1) in rats with acute lung rejection and its implication. A valid rat orthotopic left lung transplantation model (SD rat-->Wistar rat) was established by using an improved three-cuff anastomosis technique. The rats were divided into control group, CoPP (HO-1 inducer)-treated group and ZnPP (HO-1 inhibitor)- treated group. The severity of acute rejection was graded on the basis of the morphologic changes of the lung samples stained with HE. The expression of HO-1 protein in lung tissue was detected by using immunohistochemistry and Western blot, and HO-1 mRNA activity was assayed by RT-PCR. The results showed that the expression of HO-1 protein was significantly increased with the acute rejection grading in rats (P<0.01). As compared with control and ZnPP-treated groups, the severity of acute rejection was not alleviated and the grade not reduced significantly in CoPP-treated group (P>0.05). It was concluded that HO-1 protein might be involved in the pathological process of post-graft acute rejection. The expression of HO-1 protein was increased gradually with aggravation of acute rejection, and HO-1 protein might be used as an index to monitor acute rejection after lung transplantation.
Graft Rejection/*enzymology ; Heme Oxygenase (Decyclizing)/genetics ; Heme Oxygenase (Decyclizing)/*metabolism ; Lung Transplantation ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Rats, Sprague-Dawley ; Rats, Wistar

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 investigate the expression of the HO-1 gene in PC12 cells in hypoxic environment and gain further insight to the role of HO-1 in cerebral ischemia, PC12 cells were exposed to hypoxia environment (95% N2, 5% CO2) for 0.5 h, 1 h, 4 h, 8 h, 12 h, 24 h respectively. The level of HO-1 mRNA was examined by reverse transcriptase polymerase chain reaction (RT-PCR); the volume of COHb in the media were measured spectrophotometrically and the cGMP concentration of PC12 cell extracts was determined by radioimmunoassay. We found that after exposure to hypoxia for 1 h, 4 h, 8 h, 12 h, 24 h, HO-1 mRNA increased by 3%, 4%, 17%, 31% 36% as compared with that in control group respectively (P < 0.01 or P < 0.05); the COHb increased by 12%, 29%, 59%, 88%, 94% as compared with that in control group respectively (P < 0.01 or P < 0.05), and the cGMP concentration were 2.2, 3.4, 5.2, 8.1, 10.9-fold as that of the control group (P < 0.01). We are led to conclude that hypoxia induced the expression of HO-1 gene, the production of endogenous CO, and the concentration of cGMP was elevated as well.
Carbon Monoxide/metabolism ; Cell Hypoxia ; Cyclic GMP/metabolism ; Heme Oxygenase (Decyclizing)/biosynthesis ; Heme Oxygenase (Decyclizing)/*genetics ; Heme Oxygenase-1 ; PC12 Cells ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Up-Regulation

OBJECTIVES: To identify changes in blood markers of oxidative stress among dementic and healthy aged persons, and to compare levels of peripheral markers of oxidative stress between dementia of the Alzheimer's type (DAT) and vascular dementia (VD), and finally to analyze factors affecting those. DESIGN: Some antioxidants had been known to reduce the risk of dementia, while increase of 4-hydroxy-nonenal and decrease of heme oxygenase in DAT had been reported. Recently increased free radical activities were also found in VD. Therefore, this study was tried to search for a blood markers to discriminate DAT and VD. MATERIALS AND METHOD: The blood levels of total antioxidant capacity (TAC) and catalase activity of 50 patients with DAT and 50 patients with VD were compared with those of 56 healthy aged controls. In addition, variables including risk factors of dementia, degree of dementia measured by MMSE, Hasegawa Dementia Scale, GDS and CDR, and activities of daily living were also assessed. RESULTS: 1) The levels of TAC were significantly (p<0.01) lower in dementia than normal aged controls (1.47+/-0.08 mmol/L), while the catalase activities were significantly (p<0.01) higher in dementia than normal aged controls (45.61+/-11.67 kU/L). 2) The TAC levels were significantly (p<0.01) lower while the catalase significantly (p<0.01) higher in DAT (1.24+/-0.09 mmol/L, 133.42+/-58.45 kU/L respectively) than VD (1.31+/-0.08 mmol/L, 81.33+/-24.65 kU/L respectively). 3) The TAC and catalase activities were significantly (p<0.01) correlated with duration of dementia, behavior symptoms, activities of daily living, and the severity of dementia. CONCLUSIONS: Peripheral blood markers of oxidative stress were significantly different in dementia from normal aged controls. Furthermore, the difference was more severe in DAT than VD, which means the effect of oxidative stress is more in DAT than in VD. Therefore, they might be clinically useful to assess and discriminate dementia.
Activities of Daily Living ; Antioxidants ; Catalase ; Dementia* ; Dementia, Vascular ; Heme Oxygenase (Decyclizing) ; Humans ; Oxidative Stress* ; Risk Factors

Animals ; Animals, Newborn ; Carbon Monoxide ; metabolism ; Heme Oxygenase (Decyclizing) ; metabolism ; Lung ; metabolism ; Oxygen ; physiology ; Rats