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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated heme oxygenase (HO) and antioxidant status in the novel isolation and characterization of aortic endothelial cells (AECs) from a random bred wild-type strain (WILD) and selectively bred atherosclerosis-susceptible (SUS) and -resistant (RES) strains of Japanese quail. Cultured AECs expressed acetylated LDL, and were probed with endothelial and smooth muscle cell specific antibodies to confirm purity of culture. Subconfluent monolayers of RES AECs had higher HO activity than SUS AECs. At confluence, HO activity levels were similar among strains. However, RES AECs had higher HO-1 protein than WILD and SUS cells. Although ferritin protein levels were similar among the three strains, catalytic iron was higher in SUS AECs than WILD and RES cells. Glutathione levels were highest in SUS cells, intermediate in WILD, and lowest in RES, while glutathione reductase was higher in WILD and RES AECs than SUS AECs. We suggest that differences in atherosclerosis susceptibility between RES and SUS may be due, at least in part, to differences in endothelial HO and antioxidant components.
Mol Cell Biochem 2003 Oct
PMID:Heme oxygenase and antioxidant status in cultured aortic endothelial cells isolated from atherosclerosis-susceptible and -resistant Japanese quail. 1457

Diabetic cardiomyopathy is responsible for substantial morbidity and mortality in the diabetic population. Increased oxidative stress has been associated with the pathogenesis of chronic diabetic complications including cardiomyopathy. Multiple biochemical mechanisms have been proposed to increase oxidative stress in diabetes. The present study was aimed at elucidating the role of a potent oxidative and cellular stress-responsive system, the heme oxygenase (HO) system, in the heart in diabetes. Streptozotocin-induced diabetic rats were treated with a potent inhibitor of HO system, tin protoporphyrin IX (SnPPIX, 50 micromol/kg/d), and were compared with untreated diabetic and non-diabetic animals. All treatments began at the onset of diabetes, 48 h after injection of streptozotocin along with the confirmation of hyperglycemia. Animals were euthanized after 1 week and 1 month of treatment, and heart tissues were harvested. Frozen tissues were subjected to HO-1 and HO-2 mRNA expression by real-time RT-PCR and HO activity determination. Paraffin-embedded tissue sections were used for immunohistochemical analysis of HO-1 and HO-2. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) stain, a sensitive and specific marker of DNA damage, was preformed to assess damage induced by oxidative stress. In addition, tissue sections were subjected to histochemical analysis for iron. We further examined non-diabetic animals treated with a direct HO agonist, hemin (50 mg/kg/d). A possible relationship between the HO and the nitric oxide (NO) pathways was also considered by studying the mRNA levels of endothelial nitric oxide synthase (NOS) and inducible NOS, and by measuring the amount of NOS products. Our results demonstrate no significant alterations of the HO system following 1 week of diabetes. However, 1 month of diabetes caused increased oxidative stress as demonstrated by higher levels of 8-OHdG-positive cardiomyocytes (80% positive as compared to 11.25% in controls), in association with increased HO isozyme mRNA (2.7-fold increase as compared to controls) and protein expression, and augmented HO activity (759.3 as compared to 312.3 pmol BR/h/mg protein in controls). Diabetic rats further demonstrated increased number of cardiomyocytes with stainable iron. SnPPIX treatment resulted in reduced number of 8-OHdG-positive cardiomyocytes (19.5% as compared to 80% in diabetics) in parallel with reduced HO activity (569.7 as compared to 759.3 pmol BR/h/mg protein in diabetics). Non-diabetic rats treated with HO-agonist hemin exhibited abnormalities similar to diabetic rats. Our results provide the first direct demonstration that diabetes-induced oxidative stress in the heart is, in part, due to upregulated HO expression and activity. These results provide evidence of pro-oxidant activity of HO in the heart in diabetes, which could be mediated by increased redox-active iron.
J Mol Cell Cardiol 2003 Dec
PMID:Heme oxygenase in diabetes-induced oxidative stress in the heart. 1465 70

Activated macrophages express high levels of Nrf2, a transcription factor that positively regulates the gene expression of antioxidant and detoxication enzymes. In this study, we examined how Nrf2 contributes to the anti-inflammatory process. As a model system of acute inflammation, we administered carrageenan to induce pleurisy and found that in Nrf2-deficient mice, tissue invasion by neutrophils persisted during inflammation and the recruitment of macrophages was delayed. Using an antibody against 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), it was observed that macrophages from pleural lavage accumulate 15d-PGJ(2). We show that in mouse peritoneal macrophages 15d-PGJ(2) can activate Nrf2 by forming adducts with Keap1, resulting in an Nrf2-dependent induction of heme oxygenase 1 and peroxiredoxin I (PrxI) gene expression. Administration of the cyclooxygenase 2 inhibitor NS-398 to mice with carrageenan-induced pleurisy caused persistence of neutrophil recruitment and, in macrophages, attenuated the 15d-PGJ(2) accumulation and PrxI expression. Administration of 15d-PGJ(2) into the pleural space of NS-398-treated wild-type mice largely counteracted both the decrease in PrxI and persistence of neutrophil recruitment. In contrast, these changes did not occur in the Nrf2-deficient mice. These results demonstrate that Nrf2 regulates the inflammation process downstream of 15d-PGJ(2) by orchestrating the recruitment of inflammatory cells and regulating the gene expression within those cells.
Mol Cell Biol 2004 Jan
PMID:Transcription factor Nrf2 regulates inflammation by mediating the effect of 15-deoxy-Delta(12,14)-prostaglandin j(2). 1467 41

Recent studies on cultured aortic endothelial cells (AECs) from atherosclerosis-susceptible (SUS) and -resistant (RES) strains of Japanese quail suggest that differences in atherosclerosis susceptibility between RES and SUS may be due to differences in endothelial heme oxygenase (HO) and antioxidant components. We have now investigated the effects of oxidant-induced injury on HO and glutathione (GSH) in AECs from SUS and RES quail. We report that cultured AECs from SUS and RES birds differ in their response to oxidative stress. AECs from the SUS strain cells are more susceptible than those from the RES strain to oxidative stress induced by tert-butylhydroperoxide, as judged by lower HO activity, HO-1 expression, ferritin and GSH levels. Aortic endothelial cells from SUS birds also showed higher levels of catalytic iron, TBARS production and LDH release compared with RES cells, indicating that SUS AECs are more susceptible to oxidative stress than cells from the resistant strain. Furthermore, independently of genetic status, AECs from old birds have higher TBARS and lower levels of HSP70 induction than AECs from younger birds, suggesting that aging is associated with a decreased ability of AECs to respond to oxidative stress, and this may be relevant to the permissive effect of aging on the process of atherogenesis. Our results indicate that genetic factors and endogenous antioxidant systems in the blood vessel wall may be important in determining the susceptibility of vascular cells to oxidative stress and atherosclerotic plaque formation.
Mol Cell Biochem 2003 Dec
PMID:Effects of oxidant-induced injury on heme oxygenase and glutathione in cultured aortic endothelial cells from atherosclerosis-susceptible and -resistant Japanese quail. 1467 83

Scleroderma, a disease involving excessive collagen deposition, can be studied using fibroblasts cultured from affected tissues. We find that curcumin, the active component of the spice turmeric, causes apoptosis in scleroderma lung fibroblasts (SLF), but not in normal lung fibroblasts (NLF). This effect is likely to be linked to the fact that although curcumin induces the expression of the phase 2 detoxification enzymes heme oxygenase 1 and glutathione S-transferase P1 (GST P1) in NLF, SLF are deficient in these enzymes, particularly after curcumin treatment. The sensitivity of cells to curcumin-induced apoptosis and the expression of GST P1 (but not heme oxygenase 1) are regulated by the epsilon isoform of protein kinase C (PKCepsilon). SLF, which contain less PKCepsilon and less GST P1 than NLF, become less sensitive to curcumin-induced apoptosis and express higher levels of GST P1 when transfected with wild-type PKCepsilon, but not with dominant-negative PKCepsilon. Conversely, NLF become sensitive to curcumin-induced apoptosis and express lower levels of GST P1 when PKCepsilon expression or function is inhibited. The subcellular distribution of PKCepsilon also differs in NLF and SLF. PKCepsilon is predominantly nuclear or perinuclear in NLF but is associated with stress fibers in SLF. Just as PKCepsilon levels are lower in SLF than in NLF in vitro, PKCepsilon expression is decreased in fibrotic lung tissue in vivo. In summary, our results suggest that a signaling pathway involving PKCepsilon and phase 2 detoxification enzymes provides protection against curcumin-induced apoptosis in NLF and is defective in SLF. These observations suggest that curcumin may have therapeutic value in treating scleroderma, just as it has already been shown to protect rats from lung fibrosis induced by a variety of agents.
Am J Respir Cell Mol Biol 2004 Jul
PMID:Curcumin-induced apoptosis in scleroderma lung fibroblasts: role of protein kinase cepsilon. 1474 95

Endothelial damage, impaired microvascularization and immune maladaptation have been described as aetiological factors in recurrent miscarriages. We investigated the relationship between idiopathic recurrent miscarriage (IRM) and a (GT)(n) repeat microsatellite polymorphism of the gene encoding haem oxygenase 1 (HO-1), known to modulate immune functions such as T-helper (TH) cell function and to be associated with cardiovascular disease. We investigated 162 women with IRM and 129 healthy, post-menopausal controls. The length of the HO-1 (GT)(n) microsatellite was assessed by PCR and direct sequencing in all women. Results were correlated with clinical data. The distribution of genotypes was in Hardy-Weinberg equilibrium. The HO-1 (GT)(n) microsatellite repeat numbers ranged from 13 to 37, with (GT)(23) and (GT)(30) being the most common alleles in both groups. We compared alleles consisting of < or =27 GT repeats, termed class S (short) alleles and alleles consisting of >28 GT repeats, termed class L (long) alleles. Seventy per cent of women with IRM had an S allele either in heterozygous (L/S) or homozygous (S/S) form, compared to 56% of controls (P = 0.02; OR 0.54; 95% CI 0.32-0.90). With respect to S allele frequencies, we found no significant difference among women with IRM and controls [P = 0.3; odds ratio (OR) 1.23, 95% confidence interval (CI) 0.86-1.76]. Comparing women with primary and secondary IRM, no difference with respect to the length of the HO-1 (GT)(n) microsatellite was ascertained. In summary, this is the first report on a HO-1 (GT)(n) microsatellite polymorphism among women with IRM, demonstrating that the investigated polymorphism is associated with IRM in a relatively large Caucasian population.
Mol Hum Reprod 2004 Mar
PMID:The size of a microsatellite polymorphism of the haem oxygenase 1 gene is associated with idiopathic recurrent miscarriage. 1498 Nov 49

Previously it was shown that thiol antioxidants are potent inhibitors of the NO-dependent induction of heme oxygenase 1 (HOX-1) gene. However, the mechanism of HOX-1 gene down-regulation by thiol antioxidants and underlying signaling pathway remain unclear. In this study we have examined, whether the scavenging of reactive oxygen and reactive nitrogen species (ROS and RNS) is the major cause for thiol-mediated suppression of the HOX-1 induction by NO. Further, to identify the ROS family members implicated in the HOX-1 induction, we also exposed cells to various non-thiol antioxidants: dimethyl sulfoxide, dimetylthiourea, sodium salicylate, sodium formate, uric acid, catalase, and superoxide dismutase. A partial inhibition of HOX-1 induction occurred in the presence of non-polar hydroxyl radical scavengers, dimethyl sulfoxide and dimetylthiourea. The other non-thiol antioxidants were ineffective towards HOX-1 expression. Then, in order to determine, whether RNS scavenging is implicated in the HOX-1 down-regulation by thiol antioxidants, we took advantage of the capacity of suboptimal concentrations of the NO scavenger PTIO (2-phenyl-4,4,5,5-tetramethylimidazole-1-oxyl-3-oxide) to oxidize NO to nitrosating species. We showed that simultaneous cell treatment with NO donor and PTIO significantly enhanced the rate of the HOX-1 gene NO-dependent induction indicating that RNS are mediators of HOX-1 gene transcriptional activation. Thiol antioxidants completely suppressed PTIO stimulatory action. These findings imply that inhibitory action of thiol antioxidants is mediated by RNS scavenging. The study provides an approach for pharmacologycal modulation of cell response to NO and its derivatives through the use of antioxidants.
Mol Biol (Mosk)
PMID:[Effect of the antioxidants on NO-dependent induction of heme oxigenase 1 gene in U937 monocytes]. 1577 52

Case-control studies have successfully identified many significant genetic associations for complex diseases, but lack of replication has been a criticism of case-control genetic association studies in general. We selected 12 candidate genes with reported associations to chronic obstructive pulmonary disease (COPD) and genotyped 29 polymorphisms in a family-based study and in a case-control study. In the Boston Early-Onset COPD Study families, significant associations with quantitative and/or qualitative COPD-related phenotypes were found for the tumor necrosis factor (TNF)-alpha -308G>A promoter polymorphism (P < 0.02), a coding variant in surfactant protein B (SFTPB Thr131Ile) (P = 0.03), and the (GT)(31) allele of the heme oxygenase (HMOX1) promoter short tandem repeat (P = 0.02). In the case-control study, the SFTPB Thr131Ile polymorphism was associated with COPD, but only in the presence of a gene-by-environment interaction term (P = 0.01 for both main effect and interaction). The 30-repeat, but not the 31-repeat, allele of HMOX1 was associated (P = 0.04). The TNF -308G>A polymorphism was not significant. In addition, the microsomal epoxide hydrolase "fast" allele (EPHX1 His139Arg) was significantly associated in the case-control study (P = 0.03). Although some evidence for replication was found for SFTPB and HMOX1, none of the previously published COPD genetic associations was convincingly replicated across both study designs.
Am J Respir Cell Mol Biol 2005 Jul
PMID:Attempted replication of reported chronic obstructive pulmonary disease candidate gene associations. 1581 13

Exercise-induced oxidative stress (EIOS) refers to a condition where the balance of free radical production and antioxidant systems is disturbed during exercise in favour of pro-oxidant free radicals. Breath ethane is a product of free radical-mediated oxidation of cell membrane lipids and is considered to be a reliable marker of oxidative stress. The heatshock protein, haem oxygenase, is induced by oxidative stress and degrades haemoglobin to bilirubin, with concurrent production of carbon monoxide (CO). The aim of this study was to investigate the effect of maximal exercise on exhaled ethane and CO in human, canine, and equine athletes. Human athletes (n = 8) performed a maximal exercise test on a treadmill, and canine (n = 12) and equine (n = 11) athletes exercised at gallop on a sand racetrack. Breath samples were taken at regular intervals during exercise in the human athletes, and immediately before and after exercise in the canine and equine athletes. Breath samples were stored in gas-impermeable bags for analysis of ethane by laser spectroscopy, and CO was measured directly using an electrochemical CO monitor. Maximal exercise was associated with significant increases in exhaled ethane in the human, equine, and canine athletes. Decreased concentrations of exhaled CO were detected after maximal exercise in the human athletes, but CO was rarely detectable in the canine and equine athletes. The ethane breath test allows non-invasive and real-time detection of oxidative stress, and this method will facilitate further investigation of the processes mediating EIOS in human and animal athletes.
Comp Biochem Physiol A Mol Integr Physiol 2005 Jun
PMID:Effect of maximal dynamic exercise on exhaled ethane and carbon monoxide levels in human, equine, and canine athletes. 1598 82

To monitor cascade of events following alveolar extravasation of blood due to exposure to shock wave (SW), we conducted spatiotemporal assessment of myeloperoxidase (MPO), heme oxygenase 1 (HO-1), Cu,Zn superoxide dismutase (SOD-1), transferrin (TRF), 3-nitrotyrosine (3NTyr), alveolar endothelial cadherin (VE-CDH), and the CD11b adhesion molecules on leukocytes using electron microscopy, electron paramagnetic resonance spectroscopy, immunofluorescence imaging, and immunoblotting. Accumulation of HO-1, MPO, 3NTyr, and SOD-1 in HIL at the first 12 h was associated with transmigration of inflammatory leucocytes (ILK) into hemorrhagic lesions (HLs). Biodegradation of extravasated hemoglobin (exvHb) and deposition of iron in alveoli occurred at 3-56 h post-exposure and was preceded by LKC degranulation and accumulation of MPO, HO-1, and SOD-1 in HLs. These alterations were accompanied by appearance of heme and non-heme iron complexes in HLs. A significant increase in TRF-bound [Fe(3+)] (i.e., 14.6 +/- 5.3 microM vs. 4.8 +/- 2.1 microM immediately after exposure) and non-TRF complexes of [Fe(3+)] (i.e., 4.5 +/- 1.8 microM vs. < 0.3 microM immediately after exposure) occurred at 24 h post-exposure. Transmigrations of ILK, nitroxidative stress, and iron deposition in endothelial and epithelial cells were accompanied by destruction of endothelial integrity at 3 h post-exposure, and alveolar capillary network and necrotic changes in the pulmonary epithelial cells at 24-56 h post-exposure.
Exp Mol Pathol 2006 Feb
PMID:Inflammatory leukocytes and iron turnover in experimental hemorrhagic lung trauma. 1613 75


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