Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Asthma-like symptoms were induced in mice by repeated intratracheal instillation of diesel exhaust particles. Nitric oxide synthase (NOS) and superoxide dismutase (SOD) in airways were studied with immunocytochemical methods, and the role of nitric oxide was examined with the NOS inhibitor L-NMMA. Diesel exhaust particles increased the staining of cNOS in airway epithelial cells by an anti-cNOS antibody. Macrophages in the mucous membrane were stained clearly, but an anti-iNOS antibody did not stain airway epithelial cells. Diesel exhaust particles caused a 4-fold increase in the total number of macrophages, neutrophils, eosinophils, and lymphocytes in bronchoalveolar lavage fluid. Diesel exhaust particles decreased the staining of Cu, Zn-SOD, and Mn-SOD in epithelial cells by their respective anti-SOD antibodies. Diesel exhaust particles doubled the concentration of nitric oxide in exhaled air. These particles increased respiratory resistance, and this increase was suppressed by pretreatment with the NOS inhibitor L-NMMA. These results suggest that diesel exhaust particles can decrease the scavenging of O2- in airways, which may increase hyperresponsiveness. In mice exposed to diesel exhaust particles, the increase in NOS staining in airway epithelium, the increase in the nitric oxide concentration in exhaled air, and the decrease in respiratory resistance caused by L-NMMA indicate that nitric oxide may increase airway hyperresponsiveness.
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PMID:[Role of nitric oxide in asthma-like symptoms induced by diesel exhaust particles in mice]. 875 9

Superoxide dismutase (SOD) protects cells exposed to an excess of the free radical nitric oxide, by preventing the formation of peroxynitrite. Certain central cholinergic neurons express constitutive nitric oxide synthase (nNOS), and presumably they are at risk from peroxynitrite intoxication. Immunocytochemistry for choline acetyltransferase (ChAT) was combined with in situ hybridization histochemistry (ISHH) to examine whether brain cholinergic populations differ with respect to their expression of the messenger RNA molecules (mRNAs) for the manganese-dependent (Mn-SOD) and copper/zinc-dependent superoxide dismutases (Cu /Zn-SOD). The cholinergic neurons located in the reticular formation of the upper brainstem (the laterodorsal tegmental nucleus [LDTN] and the pedunculopontine nucleus [PPN]) were found to express relatively high levels of Mn-SOD mRNA, whereas cholinergic neurons located in the basal forebrain (substantia innominata [SI], diagonal band [DB], medial septum [MS], and the nucleus basalis magnocellularis [nBM]), and the striatal cholinergic interneurons expressed low to intermediate levels of Mn-SOD mRNA. The rank order of median Mn-SOD mRNA density per cholinergic cell was LDTN > PPN > SI > striatum = nBM = DB > MS. This is similar to the rank order of nNOS mRNA densities in the cholinergic cells in these regions (R = 0.9, p < 0.02). The rank order of Cu/Zn-SOD mRNA levels in cholinergic populations (DB > LDTN = PPN =MS > SI = nBM = striatum) was not correlated with nNOS mRNA (R = 0.29, P > 0.05). Thus, for cholinergic neurons, Mn-SOD may be important for protection from NO-related oxidative stress.
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PMID:Expression of superoxide dismutase messenger RNA in adult rat brain cholinergic neurons. 1063 66

We investigated the effects of aging and ischemia-reperfusion (I/R) injury on the expression and activity of nitric oxide (*NO) synthases and superoxide dismutase (SOD) isoforms. To this end we perfused excised hearts from young (6 months old) and old (31-34 months old) rats according to the Langendorff technique. The isolated hearts were, after baseline perfusion for 30 min, either subjected to 20 min of global no-flow ischemia followed by 40 min of reperfusion or were control-perfused (60 min normoxic perfusion). Both MnSOD and Cu,ZnSOD expression remained unchanged with increasing age and remained unaltered by I/R. However, SOD activity decreased from 7.55 +/- 0.1 U/mg protein in young hearts to 5.94 +/- 0.44 in old hearts (P<0.05). Furthermore, I/R led to a further decrease in enzyme activity (to 6.35 +/- 0.41 U/mg protein; P<0.05) in myocardium of young, but not in that of old animals. No changes in myocardial protein-bound 3-nitrotyrosine levels could be detected. Endothelial NOS (eNOS) expression and activity remained unchanged in aged left ventricles, irrespective of I/R injury. This was in steep contrast to peripheral (renal and femoral) arteries obtained from the same animals where a marked age-associated increase of eNOS protein expression could be demonstrated. Inducible NOS expression was undetectable either in the peripheral arteries or in the left ventricle, irrespective of age. In particular when associated with an acute pathology, which is furthermore limited to a certain time frame, changes in the aged myocardium with respect to enzymes crucially involved in maintaining the redox homeostasis, seem to be much less pronounced or even absent compared to the vascular aging process. This may point to heterogeneity in the molecular regulation of the cardiovascular aging process.
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PMID:Expression and activity patterns of nitric oxide synthases and antioxidant enzymes reveal a substantial heterogeneity between cardiac and vascular aging in the rat. 1646 9

Melatonin (MT) is an ubiquitous molecule, representing one of the phylogenetically oldest signaling mechanisms. Our previous studies demonstrated that MT and its precursor L-tryptophan (L-Trp) show strong protective effect on gastric mucosa. The aim of the present study was: 1) to assess the effect of MT and L-Trp on healing of chronic gastric ulcer and accompanying changes in gastric mucosal blood flow (GBF); 2) to study the effect of MT and L-Trp on expression of iNOS. cNOS and HSP70 in ulcerated mucosa; 3) to compare the effect of L-Trp free and L-Trp rich diet on ulcer healing and gene expression of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), superoxide dismutase (SOD), cyclooxygenase-2 (COX-2) and NFkappaB-p65 protein expression in ulcer area and intact non-ulcerated. Chronic ulcers were induced in Wistar rats by Okabe's modification of acetic acid method. Rats with chronic gastric ulcers were divided in following treatment groups: 1) vehicle (saline); 2) MT (20mg/kg-d i.p.) and 3) L-Trp (100 mg/kg i.p.). The expression of iNOS, cNOS and HSP70 protein was measured by Western blot. In separate experiments, the influence of commercially available (Bio-Serv, USA) L-Trp free diet (TFD) was compared to the L-Trp rich diet (TRD) on the course of ulcer healing was assessed. The ulcer area was measured by planimetry. The expression of TNFalpha, COX-2 and SOD mRNA in ulcerated mucosa was analyzed by RT-PCR method. MT and its precursor L-Trp significantly accelerated ulcer healing. Healing ulcerated mucosa showed increased protein expression of iNOS and HSP70 as compared to intact gastric mucosa. TFD in contrast to normal diet significantly attenuated the ulcer healing, whereas the TRD exerted opposite effects and significantly accelerated ulcer healing. This last effect was accompanied by significant decrease of TNF-alpha mRNA expression and expression of NFkB-p65 in gastric mucosa. We conclude that: 1) MT and its precursor L-Trp significantly accelerate healing of gastric ulcer; 2) L-Trp free diet significantly attenuates experimental ulcer healing and this is due to decreased synthesis of MT from L-Trp by EE cells in gastric mucosa and 3) MT shows strong anti-inflammatory effects due to inhibition of NFkappaB and TNF-alpha expression.
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PMID:Tryptophan free diet delays healing of chronic gastric ulcers in rat. 1881 28

In an experiment to clarify the involvement of oxygen radicals in lung carcinogenesis induced by diesel exhaust particles (DEP), we found that there is a strong relation between lung tumor response and formation of 8-hydroxydeoxyguanosine (8-OHdG) in lung DNA of mice administered DEP by repeated intratracheal instillation. Repeated intratracheal instillation of DEP also induced the activity of cytochrome P-450 reductase in the lungs as a representative enzyme of superoxide generation, and two types of nitric oxide (NO) synthase, cNOS and iNOS, in the lungs. On the other hand, activities of CuZn-superoxide dismutase (SOD) and Mn-SOD antioxidant enzymes were depressed by the instillation of DEP. These results suggest that generation of superoxide, hydroxyI radical, and nitric oxide are increased in epithelial cells in airways, and that the increased superoxide and nitric oxide react very easily to produce peroxynitrite (ONOO(-)). The peroxynitrite also produce hydroxyI radical. The hydroxyl radical may play an important role in carcinogenesis by DEP.
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PMID:Lung Carcinogenesis by Diesel Exhaust Particles and the Carcinogenic Mechanism Via Active Oxygens. 2636 19