Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Results are presented which support the hypothesis that adequate steady-state levels of hydrogen peroxide (H2O2) are required to overcome the effects of high catalase and glutathione peroxidase (GPx) expression for p38 mitogen-activated protein (MAP) kinase activation and tumor necrosis factor (TNF)-alpha gene expression in human alveolar macrophages stimulated with asbestos. We found significant differences in the types and amounts of reactive oxygen species generated in human blood monocytes compared with human alveolar macrophages. This difference in reactive oxygen species production is related, in part, to the differences in antioxidant enzyme expression and activity. Most importantly, catalase and GPx activities were significantly increased in alveolar macrophages compared with blood monocytes. Asbestos activated the p38 MAP kinase and induced TNF-alpha gene expression only in blood monocytes. Increasing the steady-state levels of H2O2 by using polyethylene glycol superoxide dismutase, an antioxidant that crosses the cell membrane, or aminotriazole, an irreversible inhibitor of catalase, allowed the p38 MAP kinase to be activated in alveolar macrophages. In addition, asbestos-stimulated macrophages cultured with polyethylene glycol superoxide dismutase had a significant increase in gene expression mediated by the TNF-alpha promoter. These results demonstrate that high catalase and GPx activity in human alveolar macrophages limits the effectiveness of H2O2 to act as a mediator of inflammatory gene expression.
 ...
PMID:High levels of catalase and glutathione peroxidase activity dampen H2O2 signaling in human alveolar macrophages. 1496 75

The effect of YS 51, a synthetic 1-(beta-naphtylmethyl)6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline alkaloid, on the expression of manganese-superoxide dismutase (Mn-SOD), an antioxidant enzyme, was examined in sheep pulmonary artery endothelial cells (SPAEC) and a human cervical carcinoma cell line (Hela). YS 51 alone or in combination with cytokines enhanced the expression of Mn-SOD mRNA in SPAEC and Hela cells. YS 51 also showed synergistic effects on the induction of Mn-SOD mRNA with phorbol-12-myristate-13-acetate (TPA) and/or tumor necrosis factor-alpha (TNF-alpha). In Hela cells, the induction of Mn-SOD mRNA by YS 51 was in a time- and dose-dependent manner and the expression of Mn-SOD mRNA was increased to a maximum of 4-fold in 9 h. Enhancement of Mn-SOD mRNA by YS 51 was completely abolished by actinomycin D but not cycloheximide, suggesting that the induction of Mn-SOD mRNA byYS 51 is independent of new protein synthesis. Pretreatment of curcumin, an inhibitor of c-jun N-terminal kinase (JNK), dose-dependently suppressed the induction of Mn-SOD mRNA by YS 51, but not by 2'-amino-3'-methoxyflavone (PD98059) and 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)imidazol (SB203580), inhibitors of mitogen-activated protein kinase. Also, YS 51 induced the phosphorylation activity of JNK in a time-dependent manner without affecting the phosphorylation activity of the extracellular signal-regulated kinase 1 (ERK1) and p38 MAP kinase. These results implicated that the JNK pathway appears to play a crucial role in mediating the YS 51-induced Mn-SOD gene expression, and that up-regulation of Mn-SOD would contribute to the anti-inflammatory actions mediated by YS 51.
 ...
PMID:Induction of manganese-superoxide dismutase by YS 51, a synthetic 1-(beta-naphtylmethyl)6,7-dihydroxy- 1,2,3,4-tetrahydroisoquinoline alkaloid: implication for anti-inflammatory actions. 1511 44

The anti-inflammatory properties of transforming growth factor-beta(1) (TGF-beta(1)) account for its protection against atherosclerotic plaque rupture. This study investigates whether activation of the Nrf2 (nuclear factor erythroid 2 [NF-E2]-related factor 2) transcription pathway is involved in TGF-beta(1) mediated induction of the antioxidant enzyme heme oxygenase-1 (HO-1) in smooth muscle cells (SMC). Human aortic smooth muscle cells (HAoSMC) or wild-type and Nrf2-deficient mouse (MAoSMC) aortic SMC were treated with TGF-beta(1) (2.5-10 ng/ml, 0-24 hrs). We report the first evidence that TGF-beta(1) induces Nrf2 mediated HO-1 expression and antioxidant response element activity, which was paralleled by enhanced superoxide production and expression of the NAD(P)H oxidase subunit p22(phox). TGF-beta(1) failed to induce HO-1 expression in MAoSMC derived from Nrf2-deficient mice, and HO-1 induction by TGF-beta(1) in HAoSMC was attenuated by inhibition of extracellular signal regulated kinase or c-jun-N-terminal kinase but not p38 mitogen activated protein kinase. Inhibition of NAD(P)H oxidase or scavenging of superoxide diminished HO-1 induction in response to TGF-beta(1). The oxidative stress agents glucose oxidase (GOx) and diethylmaleate enhanced TGF-beta(1) generation and HO-1 expression in HAoSMC, while antagonism of TGF-beta(1) signalling by adenoviral Smad7 overexpression attenuated their induction of HO-1. Pre-treatment of HAoSMC with TGF-beta(1) reduced nuclear translocation of the pro-apoptotic mediator p53 elicited by GOx. Our findings demonstrate that Nrf2 is a new target of TGF-beta(1) signalling in the vasculature which may contribute to the atheroprotective properties attributed to this growth factor.
 ...
PMID:Transforming growth factor-beta1 elicits Nrf2-mediated antioxidant responses in aortic smooth muscle cells. 1967 92

Heme oxygenase-1 (HO-1) is an inducible antioxidant enzyme that degrades heme to three products, biliverdin, carbon monoxide (CO), and iron ion. The present study was originally designed to characterize the HO-1 induction by Lumbricus extract as a potential cytoprotective mechanism. Through bioactivity-guided fractionation, with human HepG2 cells as the cellular detector, surprisingly, we found that arsenic was enriched in the active fractions isolated from Lumbricus extract. Arsenic speciation was further carried out by liquid chromatography with inductively coupled plasma mass spectrometry (LC/ICP-MS). Our results showed that Lumbricus extract contained two major arsenic species, arsenite (As(III) ; 53.7%) and arsenate (As(V) ; 34.2%), and six minor arsenic species. Commercial sodium arsenite (NaAsO(2) ) was used to verify the effects of Lumbricus extract on HO-1 expression and related intracellular signaling pathways. Both p38 MAP kinase and NF-E2-related factor 2 (Nrf2) pathways were found to modulate HO-1 induction by Lumbricus extract and NaAsO(2) . The cytotoxicity of arsenite was augmented by p38 MAP kinase inhibitor SB202190 and HO-1 inhibitor tin protoporphyrin IX (SnPP), whereas p38 MAP kinase inhibitor SB202190 also inhibited HO-1 induction by NaAsO(2) . These results suggest that arsenic-containing compounds are responsible for HO-1 induction by Lumbricus extract. Although the exact role of toxic arsenic compounds in the treatment of oxidative injury remains unclear, concomitant HO-1 induction may be a key mechanism to antagonize the cytotoxicity of arsenic compounds in human cells.
 ...
PMID:Concomitant induction of heme oxygenase-1 attenuates the cytotoxicity of arsenic species from lumbricus extract in human liver HepG2 cells. 2249 92