Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunocytochemical distribution of manganese superoxide dismutase (Mn-SOD) was determined in the rat hippocampus. The enzyme was localized in the mitochondria. CA1 pyramidal cells were weakly immunostained, whereas CA3 pyramidal cells were strongly reactive. These differences in the intensity of the Mn-SOD immunostaining reactions may relate to variations in the sensitivity of subfields of the hippocampus to ischemia.
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PMID:Immunocytochemical localization of manganese superoxide dismutase (Mn-SOD) in the hippocampus of the rat. 221 54

Upon exposure to a transient ischemia, the distal tubule of the kidney often escapes the severe damage which afflicts the proximal tubule. To ascertain whether this feature of the distal tubule is attributable to its intrinsic cellular properties, we focused on two pairs of unique tubule segments; distal versus proximal convoluted tubules in the superficial cortex and distal versus proximal straight tubules in the outer stripe of the outer medulla. These tubules were chosen because, firstly, they can be identified by morphology and immunostaining, and secondly, each pair has the same anatomical relationship to the circulation. Detailed morphometric analyses were performed six hours following unilateral transient ischemia in adult rats to semiquantitate the local tissue damage in these specific nephron segments. The architecture of the distal convoluted and straight tubules was remarkably well preserved, contrasting to the moderate to extensive necrotic changes seen in the proximal tubules. In search of the potential intrinsic cellular mechanism that underlies the observed difference, we examined the segmental distribution along the nephron of manganese superoxide dismutase gene transcripts by in situ hybridization. This antioxidant enzyme gene was expressed primarily in the distal tubules with contrastingly low levels of expression in the proximal tubules. Moreover, following ischemia-reperfusion, this distal tubule-dominant pattern was further accentuated immediately following reperfusion. The study indicates that the marked difference between the proximal and distal tubules in their susceptibility to injury in vivo is attributable to their intrinsic cellular properties, which include the local level of antioxidants.
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PMID:Strategic locus for the activation of the superoxide dismutase gene in the nephron. 753 59

A growing body of experimental data indicates that the "no-reflow" phenomenon is a type of reperfusion injury in skeletal muscle which may, in part, be mediated by oxygen free radicals, and thus may be attenuated by using agents that scavenge or inhibit formation of these reactive oxygen metabolites. This study was undertaken to assess the efficacy of recombinant human manganese superoxide dismutase (rhMnSOD) in reducing reperfusion injury in skeletal muscle. The specific advantage of this agent over other SOD types is a much longer plasma half-life (5 to 7 hr), allowing better equilibration between extra- and intracellular compartments. The rat cremaster model was used to study "no-reflow" in skeletal muscle. Reperfusion injury in the muscle was assessed by fluorescein dye perfusion, myocyte creatine phosphokinase (CPK) release, and contractile function in response to electrical field stimulation. Compared with untreated saline control animals, those treated with rhMnSOD after 5 hr of cremasteric ischemia, had a significantly higher percentage area of blood reflow (78 percent +/- 6 percent of normal), a greater percentage tetanic (66 percent +/- 9 percent of normal) and twitch (56 percent +/- 9 percent of normal) contractile strength, and less CPK release (21.5 percent higher than pre-reperfusion baseline CPK levels) (p < 0.05). Untreated saline control CPK release (21.5 percent higher than the prereperfusion level. Animals treated with allopurinol also had a significantly higher percentage twitch contraction (47 percent +/- 14 percent of normal) and a lower CPK release (11.1 percent of the prereperfusion value) 45 min after reperfusion than untreated saline controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Efficacy of recombinant human manganese superoxide dismutase compared to allopurinol in protection of ischemic skeletal muscle against "no-reflow". 765 Jun 47

We investigated the changes of copper/zinc superoxide dismutase (CuZn-SOD) and manganese superoxide dismutase (Mn-SOD) in the rat hippocampus after 10 min of cerebral ischemia induced by 4-vessel occlusion. The rats were allowed to survive for 4 h, 1 day, 3 days, and 7 days after ischemia. The distribution of SODs were determined by immunohistochemical staining with antibodies against rat CuZn-SOD and Mn-SOD. CA1 pyramidal neurons and granule cells of the dentate gyrus showed intense CuZn-SOD immunoreactivity, whereas CA3 and CA4 neurons showed weaker immunostaining than CA1 neurons in normal animals. The immunoreactivity was reduced by 4 h after ischemia in CA1, CA3, and CA4 neurons when no histological damage was observed. Mn-SOD immunostaining revealed more intense immunoreactivity in CA3 pyramidal neurons than in CA1 neurons in normal animals. Interneurons in the CA1 and CA3 regions and the dentate hilus also showed high Mn-SOD immunostaining. Although CA1 neurons lost Mn-SOD immunoreactivity by 1 day after ischemia, CA3 neurons and interneurons retained the immunoreactivity and preserved intact cell contour after ischemia. In addition, reactive glial cells, which were differentiated by immunocytochemical staining against glial fibrillary acidic protein for reactive astrocytes and histochemical staining for reactive microglial cells, were intensely stained for CuZn-SOD and Mn-SOD after ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An immunohistochemical study of copper/zinc superoxide dismutase and manganese superoxide dismutase in rat hippocampus after transient cerebral ischemia. 769 76

Bromocriptine, a dopamine D2 receptor agonist, has widely been used for patients with Parkinson's disease. In this study, we examined its neuroprotective effects against neuronal damage in the CA1 subfield of the hippocampus following experimental cerebral ischemia in the Mongolian gerbil. Forebrain ischemia was induced by occlusion of bilateral common carotid arteries for 3 min. Bromocriptine, at a dose of 0.3 or 3 mg/kg, was injected i.p. 30 min before the onset of ischemia. Histopathological observations showed that neuronal damage to hippocampal CA1 neurons, which was seen 7 days after ischemia in vehicle-treated animals, was prevented by bromocriptine treatment. Immunohistochemical staining for copper/zinc superoxide dismutase and manganese superoxide dismutase decreased markedly in the CA1 neurons of vehicle-treated animals 2 days after ischemia when histological neuronal destruction was not yet seen, but was well preserved in bromocriptine-treated animals. The present findings show that bromocriptine protects against ischemia-induced neuronal damage, and that the mechanism of the neuroprotection may relate to the preservation of SODs. Bromocriptine, which was recently shown to be a potent free radical scavenger, may have a potent neuroprotective action against disorders including ischemic stroke.
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PMID:Bromocriptine protects against delayed neuronal death of hippocampal neurons following cerebral ischemia in the gerbil. 775 51

Leukemia inhibitory factor (LIF) and tumor necrosis factor (TNF) have been shown to protect animals from radiation, hyperoxia, and endotoxic shock. TNF is also known to induce the expression of manganese superoxide dismutase (MnSOD) in vitro and in vivo. We therefore examined the effects of these cytokines on reperfusion injury in the isolated rabbit heart model. Rabbits were injected intravenously with 10 micrograms of either human TNF-alpha or lymphotoxin (TNF-beta), or murine TNF-alpha or murine LIF dissolved in saline. Control animals were injected with an equal volume of saline. After 24 h, hearts were isolated and perfused. Following an equilibration period, the hearts were subjected to 1 h ischemia and 1 h of reperfusion. All treated groups showed significant increases in percent recovery of developed tension (% preischemic) when compared to saline-treated control hearts. In addition there were significant decreases in lactate dehydrogenase release (LDH), accumulation of thiobarbituric acid reactive substances (TBARS), and accumulation of carbonyl proteins. These results correlate with increases in myocardial MnSOD activity. Thus, the protection from myocardial reperfusion injury seen in the pretreated group may be due to a mechanism that involves the induction of MnSOD.
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PMID:Leukemia inhibitory factor and tumor necrosis factor induce manganese superoxide dismutase and protect rabbit hearts from reperfusion injury. 776 Mar 46

We investigated immunohistochemically the localization and changes of copper/zinc superoxide dismutase (CuZn-SOD) and manganese superoxide dismutase (Mn-SOD) in the rat brain following 1 h of middle cerebral artery (MCA) occlusion. In normal brain, immunoreactivity to both SODs was observed in medium-sized neurons in the striatum and in many neurons in the neocortex. Mn-SOD was predominantly stained in cortical interneurons. The immunostaining of both SODs rapidly decreased or disappeared in neurons in the lateral segment of the striatum (ischemic center) 4 h after MCA occlusion, when the neurons were degenerating. Most neurons in the neocortex (ischemic penumbra) decreased their CuZn-SOD immunoreactivity but not Mn-SOD immunoreactivity 4 h after ischemia, when only a few neurons showed histopathological changes. CuZn-SOD immunoreactivity in almost all cortical neurons disappeared 1 day after ischemia, but Mn-SOD immunoreactivity was still preserved in interneurons, when cortical neurons showed typical pathological changes. Some cortical neurons in the boundary zone between normal and infarcted areas showed intense immunostaining to both SODs and glial SOD immunoreactivity appeared after 3 and 7 days. These results suggest that early loss of the scavenging system of free radicals may lead to neuronal damage after ischemic insult, and that induced SODs in the boundary zone between the normal and infarcted areas may act as a defense mechanism against damage.
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PMID:An immunohistochemical study of copper/zinc superoxide dismutase and manganese superoxide dismutase following focal cerebral ischemia in the rat. 805 37

The effect of ischemia-reperfusion on activity, protein and m-RNA levels of catalase, copper-zinc and manganese containing superoxide dismutases and glutathione peroxidase, the enzymes that are involved in free radical detoxification was studied in rat kidney. Ischemia alone did not alter either the activities or protein levels of superoxide dismutase and glutathione peroxidase. However, catalase activity was found to be inhibited to 82% of control. The inhibition of catalase was due to the inactivation of the enzyme as there was no significant change in enzyme protein level. Reperfusion following ischemia, however, led to a significant decrease in both the activities as well as the protein levels of all the antioxidant enzymes. The observed overall decrease in total superoxide dismutase activity was the net effect of a decrease in copper-zinc superoxide dismutase while manganese superoxide dismutase activity was found to be increased following reperfusion. This observed increase manganese superoxide dismutase activity was the result of its increased protein level. The mRNA levels for catalase, superoxide dismutases, and glutathione peroxidase were observed to be increased (100-145% of controls) following ischemia; reperfusion of ischemic kidneys, however, resulted in a significant decrease in the levels of mRNAs coding for all the enzymes except manganese superoxide dismutase which remained high. These results suggest that in tissue, the down regulation of the antioxidant enzyme system could be responsible for the pathophysiology of ischemia-reperfusion injury.
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PMID:Expression of antioxidant enzymes in rat kidney during ischemia-reperfusion injury. 828 74

To investigate whether differences in vulnerability to free radicals might underlie differences among striatal neurons in their vulnerability to neurodegenerative processes such as occur in ischemia and Huntington's disease, we have analyzed the localization of superoxide free radical scavengers in different striatal neuron types in normal rhesus monkey. Single- and double-label immunohistochemical experiments were carried out using antibodies against the enzymes copper, zinc superoxide dismutase (SOD1), or manganese superoxide dismutase (SOD2), and against markers of various striatal cell types. Our results indicate that the striatal cholinergic and parvalbumin interneurons are enriched in SOD1 and/or SOD2, whereas striatal projection neurons and neuropeptide Y/somatostatin (NPY+/SS+) interneurons express only low levels of both SOD1 and SOD2. We also found that projection neurons of the matrix compartment express significantly higher levels of SOD than those in the striosome compartment. Since projection neurons have been reported to be more vulnerable than interneurons and striosome neurons more vulnerable than matrix neurons to neurodegenerative processes, our results are consistent with the notion that superoxide free radicals are at least partly involved in producing the differential neuron loss observed in the striatum following global brain ischemia or in Huntington's disease.
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PMID:Differential abundance of superoxide dismutase in interneurons versus projection neurons and in matrix versus striosome neurons in monkey striatum. 872 Aug 60

We examined whether or not alpha 1-adrenergic stimulation increases the tolerance of the heart to ischemia using a hypoxia-reoxygenation model of cardiac myocytes. After exposure to norepinephrine (NE; 0.2 microM) for 24 h, the manganese superoxide dismutase (Mn-SOD) content and activity in the cells were increased from 0.61 +/- 0.03 to 0.87 +/- 0.04 microgram/dish and 22 +/- 1 to 55 +/- 4 U/dish, respectively. The specific activity of Mn-SOD was also increased from 36 to 63 U/microgram Mn-SOD protein after the stimulation with NE. Prazosin (2 microM) abolished the increase in Mn-SOD activity (U/mg total protein). Creatine kinase (CK) release after hypoxia (PO2 7 mmHg; 3 h)-reoxygenation (1 h) from cells pretreated with NE in the presence of propranolol and yohimbine for 24 h was attenuated by 48% compared with that from cells without NE stimulation. When antisense oligodeoxyribonucleotides to Mn-SOD were added to myocyte cultures, the increase in Mn-SOD activity (U/mg total protein) and the attenuation of CK release after the addition of NE in the presence of propranolol and yohimbine were not observed. These results suggest that alpha 1-adrenergic stimulation increases the tolerance of myocytes to hypoxia through induction and activation of Mn-SOD.
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PMID:Alpha 1-adrenergic stimulation induces cardiac tolerance to hypoxia via induction and activation of Mn-SOD. 889 28


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