Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several studies indicate that active oxygen species play an important role in the development of pulmonary disease (asbestosis and silicosis) after exposure to mineral dust. The present study was conducted to determine if inhaled fibrogenic minerals induced changes in gene expression and activities of antioxidant enzymes (AOE) in rat lung. Two different fibrogenic minerals were compared, crocidolite, an amphibole asbestos fiber, and cristobalite, a crystalline silicon dioxide particle. Steady-state mRNA levels, immunoreactive protein, and activities of selected AOE were measured in lungs 1-10 days after initiation of exposure and at 14 days after cessation of a 10-day exposure period. Exposure to asbestos resulted in significant increases in steady-state mRNA levels of manganese-containing superoxide dismutase (MnSOD) at 3 and 9 days and of glutathione peroxidase at 6 and 9 days. An increase in steady-state mRNA levels of copper, zinc-containing superoxide dismutase (CuZnSOD), was observed at 6 days. Exposure to asbestos also resulted in overall increased enzyme activities of catalase, glutathione peroxidase and total superoxide dismutase in lung. In contrast, silica caused a dramatic increase in steady-state levels of MnSOD mRNA at all time periods and an increase in glutathione peroxidase mRNA levels at 9 days. Activities of AOE remained unchanged in silica-exposed lungs. In both models, increases in gene expression of MnSOD correlated with increased amounts of MnSOD immunoreactive protein in lung and the pattern and extent of inflammation. These data indicate that the profiles of AOE are dissimilar during the development of experimental asbestosis or silicosis and suggest different mechanisms of lung defense in response to these minerals.
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PMID:Expression of antioxidant enzymes in rat lungs after inhalation of asbestos or silica. 131 5

The forms of catalase modified by treatment with dextran aldehyde were obtained and studied. Efficacy of the preparations containing native and modified forms of catalase and superoxide dismutase as well as their covalent bienzyme conjugate containing catalase-dextran aldehyde-superoxide dismutase was studied in rats with simulated silicosis. The preparations were administered into rats by means of inhalation and intraperitoneal injection. Positive protective effect exhibited a mixture of native enzymes and their covalent conjugate. The most pronounced additional effect was caused by the mixture of native catalase and superoxide dismutase as compared with modified preparation of superoxide dismutase. The preparation of bienzyme containing conjugate was less effective.
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PMID:[Antifibrosis effect of modified forms of catalase and superoxide dismutase in experimental silicosis]. 138 35

Lipid peroxidation parameters, such as malonic dialdehyde and antioxidant defense (superoxide dismutase and catalase activities) were studied in healthy individuals, miners of different occupations, working at mines of different altitudes. The studies showed that increased lipid peroxidation and decreased antioxidant defense are connected with the altitude of work and exposure to the quartz-containing dust combined with hypobaric hypoxia. Malonic dialdehyde, the final toxic product of peroxidation, is accumulated as a result of it. Increased membranous lipid peroxidation results in death and lysis of cells. It becomes the principal pathogenetic component of pneumoconiosis formation and clarifies the mechanism of its early development, comparatively fast progressing, frequency of nodular forms in miners from the high and middle altitudes. That testifies the ability of hypobaric hypoxia to produce silicosis.
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PMID:[The mechanisms of the formation of pneumoconiosis under high-altitude conditions]. 142 41

Electron spin resonance (ESR) measurements show that grinding of quartz particles in air produces silicon-based (Si. and SiO.) radicals which decay with aging in air. ESR spin trapping measurements provide evidence for the generation of hydroxyl and possibly superoxide radicals from a suspension of fresh quartz particles. The hydroxyl radical generation potential of the fresh quartz particles decreases on storing in ambient air and on the addition of catalase, superoxide dismutase, desferroxamine, or DMSO. Silica-induced lipid peroxidation also decreases on storing the fresh particles in ambient air. These findings suggest that oxygenated radicals play a role in the biochemical mechanism of pneumoconiosis in general and acute silicosis in particular.
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PMID:ESR spin trapping and cytotoxicity investigations of freshly fractured quartz: mechanism of acute silicosis. 216 64

The authors studied role of antioxidant enzymes--superoxide dismutase and catalase--in pathogenesis of experimental pulmonary silicosis in rats. Experimental silicosis was induced by intratracheal administration of quartz dust, 20 mg. Aerosols of superoxide dismutase and catalase water solutions were inhaled twice a week during first month and 5 times a week over the next 1.5 months. The results perfectly match the previous data proving quartz dust to stimulate granulocytes' release of extracellular superoxide radicals and hydrogen peroxide. The research results also demonstrate important role of agents moving one electron for reduction of oxygen in silicosis pathogenesis.
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PMID:[The influence of superoxide dismutase and catalase on the course of the pathological process in the lungs in experimental silicosis]. 985 41

Exposure to silica has been associated with progressive pulmonary inflammation and fibrosis. While the fibroblasts play an important role in the pathogenesis of silicosis, the direct interaction between silica and fibroblasts is poorly understood. We observed that silica particles stimulated intracellular ROS generation in Rat2 fibroblast, evidenced by DCFH oxidation. Silica-induced DCFH oxidation was inhibited by catalase and DPI, a flavoenzyme inhibitor. Additionally, the time course of elevation of the intracellular ROS was paralleled by the increases of MEK and ERK phosphorylation. Silica-induced ERK phosphorylation was also effectively attenuated by catalase and DPI. However, SOD enhanced the silica-induced ERK phosphorylation, indicating a role for H(2)O(2) in ERK activation. Furthermore, ERK and MEK phosphorylation are reproduced by H(2)O(2) treatment. Taken together, these results demonstrate that silica stimulates ROS production via flavoenzyme-dependent mechanism in Rat2 fibroblasts and the H(2)O(2), in turn, serves as a signal transduction element in activating MEK-ERK pathway.
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PMID:Silica-induced generation of reactive oxygen species in Rat2 fibroblast: role in activation of mitogen-activated protein kinase. 1047 90

Tumor necrosis factor alpha (TNFalpha) plays an important role in the pathogenesis of silicosis and other chronic inflammatory lung diseases. The present study investigates the role nuclear transcription factor kappaB (NF-kappaB) and oxygen free radicals in silica-induced TNFalpha production in primary alveolar macrophages and RAW 264.7 cells. Using electrophoretic mobility shift assay (EMSA) and enzyme-linked immunoadsorbent assay (ELISA), we have demonstrated that silica can induce NF-kappaB activation and TNFalpha expression in a dose-dependent manner. Transient transfection assays with a plasmid construct containing NF-kappaB binding sites linked to a reporter gene further show that silica is able to induce the transcriptional activation of NF-kappaB-dependent gene. Inhibition of NF-kappaB activation by SN50, a specific NF-kappaB blocker, abolishes silica-induced TNFalpha production. Pretreatment of the cells with catalase (H2O2 scavenger) or deferoxamine (*OH scavenger) effectively inhibits NF-kappaB and TNFalpha activation, whereas superoxide dismutase (O2 scavenger) has an opposite effect. These results indicate that silica-mediated free radical generation and NF-kappaB activation play important roles in silica-induced TNFalpha gene expression.
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PMID:Dependence of NF-kappaB activation and free radical generation on silica-induced TNF-alpha production in macrophages. 1056 91

Nuclear factor-kappaB (NF-kappaB) is a multiprotein complex that may regulate a variety of inflammatory cytokines involved in the initiation and progression of silicosis. The present study documents the ability of in vitro silica exposure to induce DNA-binding activity of NF-kappaB in a mouse peritoneal macrophage cell line (RAW264.7 cells) and investigates the role of reactive oxygen species (ROS) and/or protein tyrosine kinase in this activation. In vitro exposure of mouse macrophages to silica (100 microg/ml) resulted in a twofold increase in ROS production, measured as the generation of chemiluminescence (CL), and caused activation of NF-kappaB. Silica-induced CL was inhibited 100% by superoxide dismutase (SOD) and 75% by catalase, while NF-kappaB activation was inhibited by a variety of antioxidants (catalase, superoxide dismutase, alpha-tocopherol, pyrrolidine dithiocarbamate, or N-acetylcysteine). Further evidence for the involvement of ROS in NF-kappaB activation is that 1 mM H2O2 enhanced NF-kappaB/DNA binding and that this activation was inhibited by catalase. Specific inhibitors of protein tyrosine kinase, such as herbimycin A, genistein, and AG-494, prevented NF-kappaB activation in silica-treated cells. Genistein and AG-494 also reduced NF-kappaB activation in H2O2-treated cells. Results confirm that tyrosine phosphorylation of several cellular proteins (approximate molecular mass of 39, 58-70, and 103 kD) was increased in silica-exposed macrophages and that genistein inhibited this silica-induced phosphorylation. In contrast, inhibitors of protein kinase A or C, such as H89, staurosporin, calphostin C, and H7, had no marked inhibitory effect on silica-induced NF-kappaB activation. The results suggest that ROS may play a role in silica-induced NF-kappaB activation in macrophages and that phosphorylation events mediated by tyrosine kinase may be involved in this activation.
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PMID:Silica-induced nuclear factor-kappaB activation: involvement of reactive oxygen species and protein tyrosine kinase activation. 1083 16

Plasma vitamin C(P-VC), vitamin E(P-VE) and beta-carotene(P-beta-CAR) contents and the activities of superoxide dismutase(E-SOD), catalase(E-CAT) and glutathione peroxidase (E-GSH-Px) in erythrocyte in 73 silicosis patients and 60 healthy control subjects were measured. The average levels of P-VC, P-VE, P-beta-CAR, E-SOD, E-CAT and E-GSH-Px of patients were significantly lower than those of the controls (P < 0.001). All indexes were correlated to the course, condition and pulmonary function of silicosis patients. The results analyzed by stepwise regression showed that the correlation between course, condition and pulmonary function of patients and P-VE and E-SOD was close. The balance between oxidation and the antioxidation in silicosis patients may be disturbed, and oxygen free radical reaction may be pathologically exacerbated.
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PMID:[Study on the correlation of silicosis with antioxidant and antioxidase]. 1193 4

Workers in denim sandblasting are at a high risk of developing silicosis, an occupational lung disease caused by inhaling crystalline silica dust. The development and progress of silicosis is associated with the activation of the immune system and oxidative stress. In the former, interferon-gamma induces both neopterin release and the enzyme indoleamine [2, 3]-dioxygenase (IDO) in various cells. The determination of the kynurenine-to-tryptophan ratio and neopterin concentration has proven to be an efficient method to monitor the activation status of IDO and cellular immunity. The present study aimed to investigate whether occupational silica exposure leads to any alterations in neopterin levels, tryptophan degradation, and activities of superoxide dismutase (SOD) and catalase (CAT), agents in the antioxidant defense system. Fifty-five male denim sandblasting workers and twenty-two healthy men as controls were included. Mean neopterin and kynurenine levels, kynurenine-to-tryptophan ratio, and SOD activity were higher in subjects with silicosis compared to non-exposed controls (all, p<0.05). Neopterin levels and kynurenine-totryptophan ratios were positively correlated (p<0.05); however, no correlation was observed between length of employment and the measured parameters. Some of the measured parameters were significantly affected by the severity of the pathology. Our results suggest that silica exposure activates the cellular immune response. The increased neopterin levels and tryptophan degradation confirm the possibility of their use as an indicator of cellular immune response.
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PMID:Immunomodulation and oxidative stress in denim sandblasting workers: changes caused by silica exposure. 2408 52


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