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)

To obtain a comprehensive profile of the age-related changes of the antioxidant enzyme system in discrete brain regions (cortex, caudate-putamen, substantia nigra, thalamus), the present study involved practically the total life span of male Wistar rats (from 5 to 35 months of age). The activities of both glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase increase from 5 to 25 months of life and remain relatively constant or decrease scantily thereafter. In thalamus, the activity of total superoxide dismutase (SOD) increases from 5 to 20 months of rat life and decreases thereafter. Conversely, in both substantia nigra and caudate-putamen, enzyme activity declines steadily with age, while in parietotemporal cortex enzyme activity deteriorates from the 25th month onward. In both caudate-putamen and parietotemporal cortex, the activity of glutathione peroxidase increases from 5 to 20 months of life and remains relatively constant thereafter, while in substantia nigra the enzyme activity is practically unmodified during the life span. Furthermore, the activity of glutathione reductase in parietotemporal cortex declines from the 20th month onward, while in caudate-putamen and thalamus, enzyme activity deteriorates after an increase from 5 to 20 months of life. The interference of phosphatidylcholine and/or its metabolite(s) with the cerebral enzyme antioxidant system shows a characteristic specificity as regards both the time of onset and the enzyme activities involved, namely, SOD and glutathione reductase. The interference with SOD is related to the cytosolic form of the enzyme and affects the cortex only of 5-month-old animals and also extends to the thalamus of 15-month-old rats and all regions in 25-month-old ones.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cereb Blood Flow Metab 1989 Jun
PMID:Cerebral enzyme antioxidant system. Influence of aging and phosphatidylcholine. 271 9

To assess the role of Cu-Zn superoxide dismutase (CuZnSOD) in regulating cellular antioxidant defenses, we studied the induction of CuZnSOD mRNA by an in situ hybridization technique and of CuZnSOD protein by an immunocytochemical method in the gerbil hippocampus following 5 min of transient global ischemia. For hybridization, we synthesized 48-mer oligonucleotide (base 465-512) complementary to rat CuZnSOD mRNA. Northern blot analysis showed hybridization to a single band of molecular weight 0.65 kb. After 5 min of ischemia, the signal became stronger at 3 and 24 h and returned to the control level 3 days later. In situ hybridization histochemistry revealed an increase in labeling throughout the hippocampus, especially in the granular layer 3 h following ischemia. The increase was prolonged only in the CA1 pyramidal layer after 24 h and was eliminated within 3 days or later. Conversely, analysis by Western blotting revealed that the insult produced few effects on the induction of CuZnSOD protein. Immunocytochemistry for CuZnSOD revealed a reduced immunostaining in the CA1 pyramidal layer at 24 h of recirculation when the persistent expression of CuZnSOD mRNA was shown in the same area. Our findings suggest that the expression of endogenous CuZnSOD is temporarily stimulated by an ischemic insult without increasing the protein level. The prolonged increase in mRNA and the decrease in the protein of CuZnSOD in the CA1 neurons seem to imply an important role of the endogenous antioxidant enzyme that protects against the detrimental effects of superoxide radicals on delayed neuronal death.
J Cereb Blood Flow Metab 1993 Jan
PMID:Induction of copper-zinc superoxide dismutase in gerbil hippocampus after ischemia. 841 2

Numerous studies indicate a role for oxidative stress in the neuronal degeneration and cell death that occur during ischemia-reperfusion injury. Recent data suggest that inhibition of the proteasome may be a means by which oxidative stress mediates neuronal cell death. In the current study, the authors demonstrate that there is a time-dependent decrease in proteasome activity, which is not associated with decreased expression of proteasome subunits, after cerebral ischemia-reperfusion injury. To determine the role of oxidative stress in mediating proteasome inhibition, ischemia-reperfusion studies were conducted in mice that either overexpressed the antioxidant enzyme glutathione peroxidase [GPX 1(+)], or were devoid of glutathione peroxidase activity (GPX -/-). After ischemia-reperfusion, GPX 1(+) mice displayed decreased infarct size, attenuated neurologic impairment, and reduced levels of proteasome inhibition compared with either GPX -/- or wild type mice. In addition, GPX 1(+) mice displayed lower levels of 4-hydroxynonenal-modified proteasome subunits after ischemia-reperfusion injury. Together, these data indicate that proteasome inhibition occurs during cerebral ischemia-reperfusion injury and is mediated, at least in part, by oxidative stress.
J Cereb Blood Flow Metab 2000 Oct
PMID:Oxidative stress-associated impairment of proteasome activity during ischemia-reperfusion injury. 1104 9

The present study examined the hypothesis that spinal cord ischemic tolerance induced by hyperbaric oxygen (HBO) preconditioning is triggered by an initial oxidative stress and is associated with an increase of antioxidant enzyme activities as one effector of the neuroprotection. New Zealand White rabbits were subjected to HBO preconditioning, hyperbaric air (HBA) preconditioning, or sham pretreatment once daily for five consecutive days before spinal cord ischemia. Activities of catalase (CAT) and superoxide dismutase were increased in spinal cord tissue in the HBO group 24 h after the last pretreatment and reached a higher level after spinal cord ischemia for 20 mins followed by reperfusion for 24 or 48 h, in comparison with those in control and HBA groups. The spinal cord ischemic tolerance induced by HBO preconditioning was attenuated when a CAT inhibitor, 3-amino-1,2,4-triazole,1 g/kg, was administered intraperitoneally 1 h before ischemia. In addition, administration of a free radical scavenger, dimethylthiourea, 500 mg/kg, intravenous, 1 h before each day's preconditioning, reversed the increase of the activities of both enzymes in spinal cord tissue. The results indicate that an initial oxidative stress, as a trigger to upregulate the antioxidant enzyme activities, plays an important role in the formation of the tolerance against spinal cord ischemia by HBO preconditioning.
J Cereb Blood Flow Metab 2006 May
PMID:Hyperbaric oxygen preconditioning induces tolerance against spinal cord ischemia by upregulation of antioxidant enzymes in rabbits. 1613 55

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a transcription factor that regulates the expression of various gene products that are essential in lipid and glucose metabolism, as well as that of the peroxisome-enriched antioxidant enzyme, catalase. Activation of PPARgamma is linked to anti-inflammatory activities and is beneficial for cardiovascular diseases. However, little is known about its role in intracerebral hemorrhage (ICH). 15-Deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2) acts as a physiologic agonist for PPARgamma. In this study, we found that injection of 15d-PGJ2 into the locus of striatal hematoma increased PPARgamma-deoxyribonucleic acid (DNA) binding activity and the expression of catalase messenger ribonucleic acid (mRNA) and protein in the perihemorrhagic area. Additionally, 15d-PGJ2 significantly reduced nuclear factor-kappaB (NF-kappaB) activation and prevented neutrophil infiltration measured by myeloperoxidase (MPO) immunoassay, and also reduced cell apoptosis measured by terminal deoxynucleotide transferase dUTP nick-end labeling (TUNEL). In addition, 15d-PGJ2 reduced behavioral dysfunction produced by the ICH. Altogether, our findings indicate that injection of 15d-PGJ2 at the onset of ICH is associated with activation of PPARgamma and elevation of catalase expression, suppression of NF-kappaB activity, and restricted neutrophil infiltration. All these events predicted reduced behavioral deficit and neuronal damage.
J Cereb Blood Flow Metab 2006 Jun
PMID:15d-Prostaglandin J2 activates peroxisome proliferator-activated receptor-gamma, promotes expression of catalase, and reduces inflammation, behavioral dysfunction, and neuronal loss after intracerebral hemorrhage in rats. 1620 15

Previous studies have shown that intraparenchymal transplantation of neural stem cells (NSCs) ameliorates neurologic deficits in animals with intracerebral hemorrhage (ICH). However, massive grafted cell death after transplantation, possibly caused by a hostile host brain environment, lessens the effectiveness of this approach. We focused on the effect of oxidative stress against grafted NSCs and hypothesized that conferring antioxidant properties to transplanted NSCs may overcome their death and enhance neuroprotection after ICH. Copper/zinc-superoxide dismutase (SOD1) is a specific antioxidant enzyme that counteracts superoxide anions. We investigated whether genetic manipulation to overexpress SOD1 enhances survival of grafted NSCs and accelerates amelioration of ICH. Neural stem cells that overexpress SOD1 were administered intracerebrally 3 days after ICH in a mouse model. Histologic and behavioral tests were examined after ICH. Copper/zinc-superoxide dismutase overexpression protected the grafted NSCs via a decrease in production of reactive oxygen species. This resulted in an increase in paracrine factors released by the NSCs, and an increase in surviving neurons in the striatum and a reduction in striatal atrophy. In addition, SOD1 overexpression showed progressive improvement in behavioral recovery. Our results suggest that enhanced antioxidative activity in NSCs improves efficacy of stem cell therapy for ICH.
J Cereb Blood Flow Metab 2014 Mar
PMID:Transplantation of neural stem cells that overexpress SOD1 enhances amelioration of intracerebral hemorrhage in mice. 2432 92