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

The effects of epidermal growth factor (EGF) on Cu, Zn-superoxide dismutase (SOD) in cultured fibroblasts from rat skin exposed to superoxide anions were studied. Cross-linking of [125I]hEGF using disuccinimidyl suberate and immunoblot analysis using anti-EGF receptor antibody to crude plasma membrane fractions of fibroblasts showed that a 170 kDa EGF receptor protein was present on the membrane, as in A431 cells which over express a specific EGF receptor. The cytosolic SOD enzyme activity in fibroblasts exposed to superoxide anions 24 h after treatment with EGF plus nafamostat (NM), a potent protease inhibitor, was increased 1.6-fold compared to control-treated cells. Treatment with either EGF or NM alone, evoked little increase in SOD enzyme activity. The increase in Cu, Zn-SOD protein levels corresponded to the increase in cytosolic SOD enzyme activity in fibroblasts. The Cu, Zn-SOD mRNA level in fibroblasts treated with EGF plus NM at 3 and 6 h was higher than that of the control. Additionally, levels of [125I]hEGF degradation products released into the medium from fibroblasts exposed to superoxide anions were significantly reduced in the presence of NM. These results suggest that the stabilization of EGF by NM in culture is an important factor in the expression of its effects, and that EGF induces Cu, Zn-SOD expression by accelerating transcription of the Cu, Zn-SOD gene in cells, resulting in their protection from the effects of superoxide anion radicals.
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PMID:Effect of epidermal growth factor on Cu, Zn-superoxide dismutase expression in cultured fibroblasts from rat skin. 781 51

IL-1beta is an important mediator in the pathogenesis of type 1 diabetes both in vivo and in vitro and it has been shown to induce islet beta-cell apoptosis. Most of the IL-1beta effects seem to be mediated by NF-kappaB transcription factor activation, but its role in the induction of islet beta-cell apoptosis has not yet been clarified. Taking advantage of the protease inhibitor TPCK (N-tosyl-L-phenylalanine chloromethyl ketone), which specifically inhibits the nuclear transcription factor NF-kappaB activation, we studied the role of NF-kappaB in the rIL-1beta treated rat pancreatic islets. Our results show that TPCK blocked rIL-1beta-mediated early increase of MnSOD activity and beta-cell defence/repair protein expression, suggesting a protective role for NF-kappaB at the beginning of IL-1beta treatment; but, in a second phase, NF-kappaB induces a sustained decrease of specific beta-cell proteins like insulin, GLUT-2 and PDX-1 with a concomitant increase of aspecific proteins and iNOS transcription. The appearance of iNOS expression correlates with increased levels of nitrite + nitrate levels and appearance of mitochondrial damage detected either at morphological and biochemical level. After 36 h of IL-1beta treatment islet beta-cells begin to undergo apoptosis. Since IL-1beta induction of apoptosis is completely prevented by TCPK treatment, this finding underscores the central role of NF-kappaB in this process. Thus, our results clearly indicate that NF-kappaB regulates MnSOD genes expression and MnSOD activity, which protects islet beta-cells by IL-1beta damage. Furthermore, when the IL-1beta stress impairs islet beta-cell function, NF-kappaB activation regulates the entrance of islet beta-cell into the cell death program.
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PMID:A biphasic role of nuclear transcription factor (NF)-kappaB in the islet beta-cell apoptosis induced by interleukin (IL)-1beta. 1562 24