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)

Because reactive oxygen species have been implicated in the pathogenesis of various hyperproliferative and inflammatory diseases, the mRNA expression of the antioxidant enzyme superoxide dismutase was studied in psoriatic skin tissue. By using reverse transcription-PCR we found similar expression of copper, zinc superoxide dismutase (CuZnSOD) in the involved vs. uninvolved psoriatic skin. In contrast, the level of the manganese superoxide dismutase (MnSOD) mRNA message was consistently higher in lesional psoriatic skin as compared to adjacent uninvolved skin and healthy control skin. Parallel investigation of those cytokines that are thought to be direct or indirect inducers of the MnSOD activity revealed an increased mRNA expression of IL-1 beta, TNF-alpha, and GM-CSF in lesional psoriatic skin. To study if these cytokines exert a direct effect on dismutase expression in epidermal cells, human keratinocytes in culture were challenged with IL-1 beta, TNF-alpha, and GM-CSF. It was found that IL-1 beta and TNF-alpha, but not GM-CSF, induced the mRNA expression of MnSOD, and an additive effect was demonstrated for the two former cytokines. Further, the expression of both CuZnSOD and MnSOD transcripts was similar in cultured keratinocytes maintained at low differentiation (low Ca2+ medium) and cells forced to terminal differentiation (by high Ca2+ medium). Our results indicate that the abnormal expression of MnSOD mRNA in lesional psoriatic skin is not directly linked to the pathologic state of keratinocyte differentiation in the skin. It seems more likely that the cutaneous overexpression of MnSOD in psoriatic epidermis represents a protective cellular response evoked by cytokines released from inflammatory cells invading the diseased skin.
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PMID:Increased mRNA expression of manganese superoxide dismutase in psoriasis skin lesions and in cultured human keratinocytes exposed to IL-1 beta and TNF-alpha. 774 20

The response of the glomerular mesangial cell to reactive oxygen species (ROS) has been implicated in the pathogenesis of several forms of inflammatory renal disease. As a model of glomerular inflammation, we studied the effects of heat-aggregated immunoglobulin G (HAG), an experimental immune complex, and interleukin-1 (IL-1) on the expression of the antioxidant enzyme, manganese superoxide dismutase (MnSOD), in primary cultures of rat mesangial cells. Following exposure to either HAG or IL-1 beta, increased steady-state MnSOD mRNA levels were observed and an additive effect was seen following co-treatment with HAG and IL-1 beta. No change was observed in steady-state levels of copper/zinc superoxide dismutase mRNA with HAG or IL-1 beta exposure. RNA protein synthesis inhibitor experiments demonstrated that the HAG- and IL-1 beta-mediated increase in MnSOD mRNA was dependent on new transcription, but was independent of de novo protein synthesis. Our data on the induction of the MnSOD gene by immune complexes and IL-1 beta could indicate an important role for MnSOD in the cellular defense against ROS toxicity in glomerular inflammation.
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PMID:Heat-aggregated IgG and interleukin-1-beta stimulate manganese superoxide dismutase in mesangial cells. 877 77