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

In this study, we have used the rat model of hyperoxia to examine the molecular responses to oxidative stress in lung. We show that in addition to the antioxidant enzyme manganese superoxide dismutase, expression of a variety of stress-responsive genes including heme oxygenase-1, c-fos, c-jun, CAAT-enhancer binding protein (C/EBP)-beta, and C/EBP-delta were increased after hyperoxia. Increased c-fos, c-jun, C/EBP-beta, and C/EBP-delta mRNA expression was correlated with increased DNA binding activity of the transcription factor complexes activator protein 1 and C/EBP in tissue lysates. Because oxidative damage plays an important role in the aging process and little is known about the susceptibility of aged rats to hyperoxia, we also examined the relative tolerance of old rats to hyperoxia. Surprisingly, we observed that aged rats exhibit greater tolerance to hyperoxic stress than young rats. Old rats exhibited decreased arterial oxygen tension when compared to young rats after hyperoxia exposure. This increased tolerance coincided with decreased albumin levels in bronchoalveolar lavage and the delayed onset of activation of transcription factors and expression of oxidative stress-inducible genes in old rats. Transcription factor and stress-response gene activation may serve as useful molecular markers for oxidant lung injury.
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PMID:Molecular responses to hyperoxia in vivo: relationship to increased tolerance in aged rats. 759 40

Reactive oxygen species (ROS) are important second messengers for the induction of several genes in a variety of physiological and pathological conditions. Here we addressed the question of whether isolated, unbalanced overexpression of the antioxidant enzyme manganese superoxide dismutase (Mn-SOD) may modulate signal transduction cascades, finally leading to connective tissue degradation, a hallmark in carcinogenesis and aging. Therefore, we generated stably Mn-SOD-overexpressing fibroblasts with an up to 4. 6-fold increase in Mn-SOD activity. The Mn-SOD-overexpressing cells revealed specific resistance to the superoxide anion (O-(2))-generating agent paraquat, whereas no resistance to UVA-generated oxidative stress was found. Treatment of the Mn-SOD-overexpressing cells with various ROS-generating systems resulted (due to the enhanced dismutation of superoxide anion to hydrogen peroxide) in an up to 9.5-fold increase in matrix-degrading metalloprotease-1 (MMP-1) mRNA levels. A similar increase in MMP-1 mRNA was also seen when the intracellular H(2)O(2) concentration was increased by the inhibition of different H(2)O(2)-detoxifying pathways. Furthermore, prooxidant conditions led to a strong induction of c-jun and c-fos mRNA levels resulting in a 4-fold higher transactivation of the transcription factor AP-1 in the Mn-SOD-overexpressing cells. Collectively, we have found that enhanced Mn-SOD activity, via an unbalanced H(2)O(2) overproduction and detoxification, induces MMP-1 mRNA levels, and this effect is at least partly mediated by the DNA recognition sequence AP-1.
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PMID:Stable overexpression of manganese superoxide dismutase in mitochondria identifies hydrogen peroxide as a major oxidant in the AP-1-mediated induction of matrix-degrading metalloprotease-1. 1046 29

A model of rabbit tracheal epithelial (RTE) cells in primary culture was used to characterize specific and repair responses of airway epithelial cells to oxidative stress. Two well-known reactive oxygen species (ROS) generating systems were used: H(2)O(2) alone or in combination with Fe(2+) to produce the hydroxyl radical. RTE cells exhibited lipid peroxidation when exposed to H(2)O(2) + Fe(2+). Moreover, catalase (CAT) activity decreased after a 1-hour treatment in 3-day-old cultures but increased in 7-day-old cultures which have higher antioxidant enzyme activities. Superoxide dismutase (SOD) activity was never affected. In addition, RTE cells displayed a repair response leading to squamous metaplasia. H(2)O(2) + Fe(2+) treatment resulted in a time-dependent increase in the steady-state level of c-myc mRNA while c-jun and c-fos were not activated. Moreover, a chronic exposure induced the expression of the squamous phenotype characterized by the expression of the cytokeratin 13 confirmed both at the message and protein levels. RTE cells in primary culture react early to H(2)O(2) + Fe(2+) exposure by an increase in c-myc expression and by modifications in CAT activity. Further, a lipid peroxidation occurs and the tracheal epithelium evolves to squamous metaplasia.
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PMID:Responses of the rabbit tracheal epithelium in vitro to H(2)O(2)-induced oxidative stress. 1079 94

Astrocytes play an important role in the homeostasis of the CNS both in normal conditions and after ischemic injury. The swelling of astrocytes is observed during and several seconds after brain ischemia. Then ischemia stimulates sequential morphological and biochemical changes in glia and induces its proliferation. Reactive astrocytes demonstrate stellate morphology, increased glial fibrillary acidic protein (GFAP) immunoreactivity, increased number of mitochondria as well as elevated enzymatic and non-enzymatic antioxidant activities. Astrocytes can re-uptake and metabolize glutamate and in this way they control its extracellular concentration. The ability of astrocytes to protect neurons against the toxic action of free radicals depends on their specific energy metabolism, high glutathione level, increased antioxidant enzyme activity (catalase, superoxide dismutase, glutathione peroxidase) and overexpression of antiapoptotic bcl-2 gene. Astrocytes produce cytokines (TNF-alpha, IL-1, IL-6) involved in the initiation and maintaining of immunological response in the CNS. In astrocytes, like in neurones, ischemia induces the expression of immediate early genes: c-fos, c-jun, fos B, jun B, jun D, Krox-24, NGFI-B and others. The protein products of these genes modulate the expression of different proteins, both destructive ones and those involved in the neuroprotective processes.
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PMID:Role of astrocytes in pathogenesis of ischemic brain injury. 1471 74