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

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

AIMTo investigate antimalarial mechanism of Qinghaosu ( QHS) and its derivatives.

METHODSThe electronic structure of QHS and its derivatives were completely optimized and calculated at B3LYP/6-31G * level, while the route was at HF/STO-3G level.

RESULTSThe peroxide bridge is the active center of QHS and induced by ferrous iron to produce cyclic product.

CONCLUSIONHeme can link with QHS derivatives.

Antimalarials ; chemistry ; isolation & purification ; Artemisia ; chemistry ; Artemisinins ; chemistry ; isolation & purification ; Electron Transport ; Free Radicals ; chemistry ; Heme ; chemistry ; Models, Chemical ; Peroxides ; chemistry ; Plants, Medicinal ; chemistry ; Quantum Theory

Reactive oxygen species have been known to be an important factor in the pathogenesis of hypertension. Bilirubin, one of the metabolites of heme degraded by heme oxygenase, is a potent anti-oxidant. We verified the effect of serum bilirubin level on the incidence of hypertension in normotensive subjects. We grouped 1,208 normotensive subjects by the criterion of the highest quintile value of serum bilirubin, 1.1 mg/dL. The incidence of hypertension was higher in group 1 with bilirubin less than 1.1 mg/ dL than in group 2 with bilirubin 1.1 mg/dL or more (186/908 vs. 43/300, p=0.018). The relative risk for hypertension was 0.71 (95% confidence interval, 0.51-0.99), p=0.048 in group 2 compared to group 1 by Cox's proportional hazard model. Among the groups stratified by gender, smoking, and liver function status, the group 2 showed a lower risk of hypertension in females and in non-smokers. In conclusion, a mild increase within the physiological range of serum bilirubin concentration was negatively correlated with the incidence of hypertension. The effect of bilirubin on the development of hypertension was more evident in females and in non-smokers.
Adult ; Bilirubin/*blood ; Blood Pressure ; Female ; Heme/chemistry ; Heme Oxygenase (Decyclizing)/metabolism ; Humans ; Hypertension/*blood/*epidemiology ; Korea ; Male ; Middle Aged ; Proportional Hazards Models ; Questionnaires ; Risk ; Smoking

OBJECTIVETo investigate the effects of Salvia miltiorrhiza (SM) extracts on the expression of heme oxygenase-1 (HO-1) and nitric oxide synthase (NOS) in small pulmonary arteries (SPAs) of rats with chronic hypoxia.

METHODSAfter two weeks of hypoxia, rats were treated with diltiazem, and small, median, and large doses of SM extracts. The lungs were tested for the expression and distribution of HO-1, endothelial NOS (eNOS) and inducible NOS (iNOS) by using immunohistochemistry and Western blot method.

RESULTSMedian and large doses of SM extracts significantly reduced hypoxia-induced media thickening in the SPAs (similar with diltiazem), recovered repaired ultrastructure injury, decreased HO-1 and iNOS levels, and increased eNOS expression in the SPAs.

CONCLUSIONSMedian and large doses of SM extracts play significant roles in inhibiting structural remodeling in rats with hypoxic pulmonary hypertension. These effects might attribute to the suppression of HO-1 and iNOS, and the promotion of eNOS expression under the conditions of hypoxia.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Heme Oxygenase (Decyclizing) ; metabolism ; Heme Oxygenase-1 ; Hypertension, Pulmonary ; drug therapy ; enzymology ; Hypoxia ; complications ; Nitric Oxide Synthase ; metabolism ; Rats ; Rats, Wistar ; Salvia miltiorrhiza ; chemistry

OBJECTIVETo study the protective effect of Blueberry against rat hepatic fibrosis and the effect of Blueberry on HO-1 expression patterns.

METHODSA total of 45 SD rats were randomly divided into five groups namely control group (group A), model group (group B), blueberry group (group C), Dan-shao-hua-xian (DSHX) capsule group (group D) and blueberry +Dan-shao-hua-xian group (group E). Fibrous liver models in rats were induced by subcutaneous injection of CCl4 and high-lipid/low-protein diet for 8 weeks except the control group which accepted saline alone. The level of alanine aminotransferase (ALT) in serum was examined. The activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenates were determined. by the xanthine oxidase method and the thiobarbituric acid method. The pathology of hepatic fibrosis was evaluated by hematoxylin and eosin (H and E) staining. The Expression of HO-1 was detected by real-time RT-PCR, immunohistochemical techniques and western blotting.

RESULTSSerum ALT levels in every prevention group was lower than the group B [(149.44+/-16.51), (136.88+/-10.07), (127.38+/-11.03) vs (203.25+/-31.62) U/L, F = 92.498, P < 0.05], the SOD of liver homogenate in prevention group was significantly higher and the MDA was lower compared with the group B [SOD: (1.36+/-0.09), (1.42+/-0.13), (1.50+/-0.15) vs (1.08+/-0.19) U/mg, F = 13.671, P < 0.05; MDA: (0.294+/-0.026), (0.285+/-0.025), (0.284+/-0.028) vs (0.335+/-0.056) nmol/mg, F = 20.809, P < 0.05]. The pathological stages of hepatic fibrosis were all significantly reduced in prevention group (Chi2 test = 24.956, P < 0.05). Compared with group A, the mRNA and protein expressions of HO-1 were elevated (F = 4.549, 22.926, P < 0.05) in group B and increased in group C-E, but there is no significant difference existed.

CONCLUSIONBlueberry may have preventive and protective effects on CCl4-induced hepatic fibrosis by reducing lipid peroxidation. However, these effects may not be related to the activation of HO-1 during long-term of CCl4.

Animals ; Blueberry Plants ; chemistry ; Carbon Tetrachloride ; toxicity ; Drugs, Chinese Herbal ; pharmacology ; Heme Oxygenase (Decyclizing) ; blood ; Liver Cirrhosis, Experimental ; blood ; Male ; Malondialdehyde ; blood ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo compare the distribution of heme oxygenase-2 and concentration of carbon monoxide in rat penile tissue of 8, 16 and 24 months and investigate the relationship between the system of HO-2/CO and aging.

METHODSUsing SABC immunohistochemistry staining, image analysis system and the method of carboxyhemoglobin standard curve, the distribution of heme oxygenase-2 and concentration of carbon monoxide in different month rat penile tissues were investigated.

RESULTSThe penile arteries were surrounded by HO-2 positive cells, which were also seen in the trabecular meshwork of smooth muscle. Compared with other part of penile, the penile arteries adventitia and the endothelial cells of cavernous exhibited darker staining. With the increasing of rat's living month the staining of penile tissues turned faint and the concentration of carbon monoxide in tissue decreased( P < 0.05 ). The imaging analysis system showed that the older the rat was the less HO-2 positive compositions contained (P < 0.05).

CONCLUSIONWith aging the decreasing concentration of HO-2 leads to the downfgt-regulation in rat penile tissue.

Aging ; metabolism ; Animals ; Carbon Monoxide ; analysis ; metabolism ; Down-Regulation ; Heme Oxygenase (Decyclizing) ; analysis ; metabolism ; Image Processing, Computer-Assisted ; Immunohistochemistry ; Male ; Penis ; chemistry ; metabolism ; Rats ; Rats, Wistar ; Staining and Labeling

Heme is a key cofactor in aerobic life, both in eukaryotes and prokaryotes. Because of the high reactivity of ferrous protoporphyrin IX, the reactions of heme in cells are often carried out through heme-protein complexes. Traditionally studies of heme-binding proteins have been approached on a case by case basis, thus there is a limited global view of the distribution of heme-binding proteins in different cells or tissues. The procedure described here is aimed at profiling heme-binding proteins in mouse tissues sequentially by 1) purification of heme-binding proteins by heme-agarose, an affinity chromatographic resin; 2) isolation of heme-binding proteins by SDS-PAGE or two-dimensional electrophoresis; 3) identification of heme-binding proteins by mass spectrometry. In five mouse tissues, over 600 protein spots were visualized on 2-DE gel stained by Commassie blue and 154 proteins were identified by MALDI-TOF, in which most proteins belong to heme related. This methodology makes it possible to globally characterize the heme-binding proteins in a biological system.
Animals ; Carrier Proteins ; biosynthesis ; genetics ; Electrophoresis, Gel, Two-Dimensional ; Electrophoresis, Polyacrylamide Gel ; Heme ; chemistry ; Hemeproteins ; biosynthesis ; genetics ; Mass Spectrometry ; Mice ; Mice, Inbred ICR ; Protein Binding ; Proteins ; chemistry ; Proteome ; Proteomics ; methods ; Sepharose ; chemistry ; Tissue Distribution

OBJECTIVETo study the expression and the role of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS) in preterm rats with hyperoxia-induced lung injuries.

METHODSSixty-four three-day-old preterm Sprague-Dawley rats were randomly assigned to a hyperoxia group (90% oxygen exposure) and a control group (room air exposure), with 32 rats in each group. After 3 days or 7 days of exposure, the lung activity of HO-1 and nitric oxide (NO) contents in bronchoalveolar lavage fluid (BALF), pulmonary histopathologic changes, and the cellular distribution and expression of HO-1 and iNOS in the lungs were measured.

RESULTSAfter 3 days and 7 days of exposure, the hyperoxia group showed acute lung injuries characterized by the presence of hyperaemia, red cell extravasation and inflammatory infiltration. The NO contents in BALF and the iNOS expression in the lungs increased significantly in the hyperoxia group compared with those in the control group 3 and 7 days after exposure. The expression of HO-1 in macrophages in the lungs increased significantly in the hyperoxia group compared with that in the control group 3 and 7 days after exposure. The NO contents in BALF and the iNOS and HO-1 expression in the lungs increased significantly 7 days after hyperoxia exposure compared with 3 days after hyperoxia exposure.

CONCLUSIONSiNOS and HO-1 levels in the lungs increase in preterm rats with hyperoxia-induced lung injuries, suggesting that iNOS and HO-1 may play roles in hyperoxia-induced pulmonary injuries.

Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; Female ; Heme Oxygenase (Decyclizing) ; analysis ; physiology ; Hyperoxia ; complications ; enzymology ; Lung ; enzymology ; Lung Injury ; etiology ; Male ; Nitric Oxide Synthase Type II ; analysis ; physiology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the changes in the expression of HIF-1alpha in rat superior mesenteric artery (SMA) tissue after hypovolemic shock (HS), and its relationship with the pathogenesis of vascular hyporeactivity.

METHODSOne hundred and twelve SD rats were used in the study, and they were randomly divided into HS group (n = 56) and treatment group (n = 56, with intraperitoneal injection of 9 microg/kg oligomycin 4 h before the experiment). Arterial blood of the rats in each group were harvested at 0.0, 0.5, 1.0, 2.0, 3.0, 4.0, 6.0 post-injury hour (PIH), respectively,with 8 rats at each time-points. Then the rats were sacrificed and superior mesenteric arteries (SMA) were harvested. Other 8 rats without any treatment served as normal controls. The changes in mRNA expression of HIF-1alpha, inducible nitric oxide synthase (iNOS) and hemeoxygenase 1 (HO-1) were determined with RT-PCR. The contraction of vascular ring of SMA to gradient concentration of norepinephrine (NE) was measured with ex vitro vascular ring tension determination method. The plasma content of carbon monoxide and nitric oxide were measured with sodium dithionite reduction method and nitrate reductase method, respectively.

RESULTSCompared with normal controls, Vascular reactivity of SMA in HS group increased compensatorily during early stage of HS (0.0 -1.0 h), and peaked at 0.5 h. The pD2 ( - log[ NE] ) of NE decreased, but the maximal contraction (Emax) was above the normal level during 0.0 - 1.0 PIH (P < 0.01). During the middle and late shock stage, the vascular reactivity decreased gradually. The Emax decreased, pD2 increased, and the Emax was below the normal level at 4.0 PIH (P < 0.01). The increase of vascular reactivity in treatment group was partially inhibited during early stage after injury (P < 0.01). The Emax was (2.01 +/- 0. 22) g/mg at 0.5 PIH, which was obviously lower than that in HS group [(2.96 +/- 0.18) g/mg , P < 0.05]. In decompensated period of HS, the vascular reactivity was improved mildly, which exhibited obvious difference compared with that in HS group at 4.0 and 6.0 PIH (P < 0.05 or P < 0.01). HIF-1alpha mRNA expression in HS group exhibited a time-dependent increase following HS, and peaked at 4.0 PIH (P < 0.01), and the iNOS and HO-1 mRNA expression were also gradually increased, reaching the peak value at 2.0 and 4.0 PIH, respectively (P < 0.01). The plasma content of CO and NO in whole blood were gradually increased following the shock process when compared with those in normal control group, while the CO content in whole blood in treatment group maintained normal, and the plasma content of NO was obviously decreased compared with that in control group.

CONCLUSIONHS can elicit a dual-phase change in vascular reactivity as previously described. HIF-1alpha plays an important role in the occurrence of vascular hyporeactivity following HS.

Animals ; Blood Vessels ; metabolism ; Carbon Monoxide ; blood ; Heme Oxygenase-1 ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Nitric Oxide ; blood ; Nitric Oxide Synthase ; metabolism ; Plasma ; chemistry ; Rats ; Rats, Sprague-Dawley ; Shock, Hemorrhagic ; metabolism