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

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

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

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

Animals ; Antihypertensive Agents ; pharmacology ; Heme Oxygenase (Decyclizing) ; drug effects ; metabolism ; Losartan ; pharmacology ; Rats ; Water-Electrolyte Balance

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

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.
Animals ; Carbon Monoxide ; metabolism ; Cell Hypoxia ; Cyclic GMP ; metabolism ; Heme Oxygenase (Decyclizing) ; biosynthesis ; genetics ; Heme Oxygenase-1 ; PC12 Cells ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Up-Regulation

OBJECTIVESTo observe the function of heme oxygenase (HO) in the lung damage in hepatic cirrhosis rats.

METHODSLiver cirrhosis model rats were made by CCl4. Lung samples taken from normal and cirrhotic rats were examined for HO-1 and HO-2 protein and expression distribution with immunohistochemical staining and western blot.

RESULTSLiver cirrhosis model rats were successfully constructed. There was a notable increase of HO-1 staining (0.062+/-0.021 vs 0.185+/-0.044, t=11.24, P<0.01) and protein expression (0 vs 5294.92+/-46.02, t=11.45, P<0.01) in both vascular and bronchial smooth muscle cells and endothelium in cirrhotic rats, however, no statistical difference of HO-2 between cirrhotic and normal rats was observed.

CONCLUSIONThe HO-CO pathway is probably involved in the pathogenesis of lung damage in hepatic cirrhosis rats.

Animals ; Carbon Tetrachloride Poisoning ; Heme Oxygenase (Decyclizing) ; analysis ; biosynthesis ; Heme Oxygenase-1 ; Liver Cirrhosis, Experimental ; enzymology ; Lung ; enzymology ; Male ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley

AIMTo observe the dynamic changes of heme oxygenase-1 (HO-1) mRNA and protein express in subfornical organ in rats with experimental allergic encephalomyelitis (EAE) to confirm that SFO is one of the sites for blood-bearing signaling molecules entering into brain.

METHODSEAE was induced by CFA-GPSCH on Wistar rats, we observed the levels of HO-1 mRNA and its protein expression with immunohistochemistry and in situ hybridization technology on 1 d, 7 d, 14 d, and 21 d after EAE induction in SFO of rats. The relationship between HO-1 and symptoms of EAE was also investigated.

RESULTSThe expression levels of HO-1 mRNA and its protein expression were very low in the brains of the control group, whereas they were enhanced gradually with pathological course in the brain and onsets of symptoms, signs of EAE. On 1 d after induction of EAE, positive cells of HO-1 mRNA and its protein expression were observed at SFO, but the labeled cells were rarely seen in the other brain regions. On 7 d, the positive cells increased markedly. On 14 d the levels of HO-1 mRNA and its protein expression in the brains reached the peak, the positive cells of HO-1 were mainly located at the choroid plexuses and SFO, as well as the regions around "sleeve-like" lesion foci, all of which were coincident with the locations of lesions of EAE. The changes of incidence, symptom, reduction of the body weight, and pathology lesions of EAE in rat brains were the most significant. On 21 d, the levels of HO-1 mRNA and its protein expression reduced gradually, which was in parallel with remitted symptoms of EAE. When a specific inhibitor of HO-1, Snpp9, was applied, the symptoms and pathological lesions of EAE in brains were mitigated markedly.

CONCLUSIONSFO may be one of the earliest sites for blood-bearing signaling molecules entering into brain. The dynamic changes of HO-1 mRNA and its protein expression are in parallel with the changes of symptoms and pathological lesions of EAE in the brains. Application of some inhibitors of HO-1 may be one of potential therapeutic methods for prevention and treatment of EAE.

Animals ; Encephalomyelitis, Autoimmune, Experimental ; metabolism ; Female ; Heme Oxygenase (Decyclizing) ; genetics ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; Subfornical Organ ; metabolism

OBJECTIVETo investigate whether formalin inflammatory pain can induce the change in heme oxygenase-1 (HO-1) expression in the spinal cord of rats or not and the time course character.

METHODS42 SD rats were divided into 7 groups (n = 6): control formalin 6 h, formalin 12 h, formalin 1 d, formalin 2 d, formalin 3 d and formalin 7 d groups. Rats were subcutaneously injected with 0.2 ml 0.5% formalin into the ventral surface of right hind paw to induce periphery inflammatory pain. The immunohistochemistry was used to observe the expression of HO-1 protein in laminae I - II of the spinal cord dorsal horn and the area around canalis centralis of the I5 spinal segment of rats.

RESULTSThere are rare HO-1 immunoreactive cells in the laminae I - II of the dorsal horn and the area around canalis centralis of the I5 spinal segment of rats of control group and HO-1 immunoreactive cells were light in staining degree. Comparing with control group, the numbers of HO-1 immunoreactive cells in the I - II laminae of dorsal horn and area around canalis centralis were increased in the rats at 6 h after formalin injection. The number and staining degree of HO-1 immunoreactive cells were further increased at 12 h and peaked at 1 d after formalin injection. They didn't return to normal level at the 7th day. There were no difference in right and left dorsal horn in the number and staining degree of HO-1 immunoreactive cells at the same time after formalin injection.

CONCLUSIONFormalin inflammatory pain induced increased expression of HO-1 in the spinal cord dorsal horn and the area around canalis centralis of rats. At 1 d after injection of formalin, the increased expression of HO-1 was the most obviously.

Animals ; Formaldehyde ; adverse effects ; Heme Oxygenase (Decyclizing) ; metabolism ; Male ; Pain ; metabolism ; Pain Measurement ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; metabolism