1.Heme Oxygenase-1: Its Therapeutic Roles in Inflammatory Diseases.
Immune Network 2009;9(1):12-19
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
2.Heme Oxygenase-1: Its Therapeutic Roles in Inflammatory Diseases.
Immune Network 2009;9(1):12-19
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
3.Expression of heme oxygenase enzyme in the testis tissue and azoospermia.
Yan CHI ; Xiang-Ming MAO ; Xin-Zong ZHANG ; Feng-Bin ZHANG ; Yu-Chun GU ; Cheng-Liang XIONG
National Journal of Andrology 2011;17(8):712-716
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
4.Change of Expression and Activity of Heme Oxygenase-1 in Rat Corpus Cavernosum during Low-flow Priapism.
Woo Jin KIM ; Hang Ki JUNG ; Jae Hun JUNG ; Sung Chul KAM ; Jeong Seok HWA ; Jae Seog HYUN
Korean Journal of Andrology 2004;22(2):81-86
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
5.Induction of the expression of heme oxygenase gene in PC12 cells by hypoxia.
Zheng, XUE ; Dengji, PAN ; Suming, ZHANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2002;22(4):299-301
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
6.Expression and location of heme oxygenase in the lung of experimental cirrhotic rats.
Chinese Journal of Hepatology 2003;11(10):599-601
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
7.Induction of the expression of heme oxygenase gene in PC12 cells by hypoxia.
Zheng XUE ; Dengji PAN ; Suming ZHANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2002;22(4):299-301
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
8.Low Dose Carbon Monoxide Inhalation Prevents Chronic Allograft Nephropathy following Kidney Transplantation in Rats. Heme Oxygenase-1 Derivatives Study I.
Journal of the Korean Surgical Society 2008;74(5):323-329
PURPOSE: Carbon monoxide (CO), a product of heme catalysis by heme oxygenase (HO-1, HO-2, HO-3), induces cytoprotection against ischemia/reperfusion (I/R) injury in a variety of organs such as the heart, lungs, kidneys, and liver. I examined whether CO would prevent chronic allograft nephropathy (CAN) associated with renal transplantation in rats. METHODS: Kidneys from male Fisher rats were perfused and harvested for transplantation. Lewis rats were used as recipients. After reperfusion of the implanted kidney, the recipient's remaining kidney was removed promptly. Recipients were then immediately treated with the indicated regimen of CO in a Plexiglas exposure chamber. At 90 days after transplantation, the animals were sacrificed for graft histopathology, serum creatinine, and blood urea nitrogen (BUN) as markers of kidney function. RESULTS: CAN in rats was achieved using a model of Fisher-to-Lewis transplants and evaluating kidney function over the 90 days following transplantation. CO administered at 100 ppm for 1 hr/day for 7 days prevented CAN at 90 days post-transplant. CO also decreased histopathological alterations, including leukocyte infiltration and cell death. CONCLUSION: These data expand our understanding of the protective effects of low-dose CO inhalation in preventing the development of chronic fibro-inflammatory changes associated with chronic allograft nephropathy and allow us to devise methods for improving long-term renal allograft function.
Animals
;
Blood Urea Nitrogen
;
Carbon
;
Carbon Monoxide
;
Catalysis
;
Creatinine
;
Cytoprotection
;
Heart
;
Heme
;
Heme Oxygenase (Decyclizing)
;
Heme Oxygenase-1
;
Humans
;
Inhalation
;
Kidney
;
Kidney Transplantation
;
Leukocytes
;
Liver
;
Lung
;
Male
;
Polymethyl Methacrylate
;
Rats
;
Reperfusion
;
Transplantation, Homologous
;
Transplants
9.The Effect of ABO Blood Groups, Hemoglobinopathy, and Heme Oxygenase-1 Polymorphisms on Malaria Susceptibility and Severity
Jiraporn KUESAP ; Kesara NA-BANGCHANG
The Korean Journal of Parasitology 2018;56(2):167-173
Malaria is one of the most important public health problems in tropical areas on the globe. Several factors are associated with susceptibility to malaria and disease severity, including innate immunity such as blood group, hemoglobinopathy, and heme oxygenase-1 (HO-1) polymorphisms. This study was carried out to investigate association among ABO blood group, thalassemia types and HO-1 polymorphisms in malaria. The malarial blood samples were collected from patients along the Thai-Myanmar border. Determination of ABO blood group, thalassemia variants, and HO-1 polymorphisms were performed using agglutination test, low pressure liquid chromatography and polymerase chain reaction, respectively. Plasmodium vivax was the major infected malaria species in the study samples. Distribution of ABO blood type in the malaria-infected samples was similar to that in healthy subjects, of which blood type O being most prevalent. Association between blood group A and decreased risk of severe malaria was significant. Six thalassemia types (30%) were detected, i.e., hemoglobin E (HbE), β-thalassemia, α-thalassemia 1, α-thalassemia 2, HbE with α-thalassemia 2, and β-thalassemia with α-thalassemia 2. Malaria infected samples without thalassemia showed significantly higher risk to severe malaria. The prevalence of HO-1 polymorphisms, S/S, S/L and L/L were 25, 62, and 13%, respectively. Further study with larger sample size is required to confirm the impact of these 3 host genetic factors in malaria patients.
Agglutination Tests
;
Blood Group Antigens
;
Chromatography, Liquid
;
Healthy Volunteers
;
Heme Oxygenase (Decyclizing)
;
Heme Oxygenase-1
;
Heme
;
Hemoglobin E
;
Hemoglobinopathies
;
Hemoglobins
;
Humans
;
Immunity, Innate
;
Malaria
;
Plasmodium vivax
;
Polymerase Chain Reaction
;
Prevalence
;
Public Health
;
Sample Size
;
Thalassemia
10.Heme Oxygenase-1 Induced by Aprotinin Inhibits Vascular Smooth Muscle Cell Proliferation Through Cell Cycle Arrest in Hypertensive Rats.
Hyoung Chul CHOI ; Kwang Youn LEE ; Dong Hyup LEE ; Young Jin KANG
The Korean Journal of Physiology and Pharmacology 2009;13(4):309-313
Spontaneous hypertensive rats (SHR) are an established model of genetic hypertension. Vascular smooth muscle cells (VSMC) from SHR proliferate faster than those of control rats (Wistar-Kyoto rats; WKY). We tested the hypothesis that induction of heme oxygenase (HO)-1 induced by aprotinin inhibits VSMC proliferation through cell cycle arrest in hypertensive rats. Aprotinin treatment inhibited VSMC proliferation in SHR more than in normotensive rats. These inhibitory effects were associated with cell cycle arrest in the G1 phase. Tin protoporphyrin IX (SnPPIX) reversed the anti-proliferative effect of aprotinin in VSMC from SHR. The level of cyclin D was higher in VSMC of SHR than those of WKY. Aprotinin treatment downregulated the cell cycle regulator, cyclin D, but upregulated the cyclin-dependent kinase inhibitor, p21, in VSMC of SHR. Aprotinin induced HO-1 in VSMC of SHR, but not in those of control rats. Furthermore, aprotinin-induced HO-1 inhibited VSMC proliferation of SHR. Consistently, VSMC proliferation in SHR was significantly inhibited by transfection with the HO-1 gene. These results indicate that induction of HO-1 by aprotinin inhibits VSMC proliferation through cell cycle arrest in hypertensive rats.
Animals
;
Aprotinin
;
Cell Cycle
;
Cell Cycle Checkpoints
;
Cell Proliferation
;
Cyclin D
;
G1 Phase
;
Heme
;
Heme Oxygenase (Decyclizing)
;
Heme Oxygenase-1
;
Hypertension
;
Metalloporphyrins
;
Muscle, Smooth, Vascular
;
Phosphotransferases
;
Protoporphyrins
;
Rats
;
Tin
;
Transfection