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)

We have studied the long-term effects of nicotinamide (NIC) on the synthesis of NO by insulin producing cells. NIC delays the formation of nitrite by interleukin (IL)-1 beta-(IL-1, 25 U/ml)-stimulated RINm5F cells, and previous exposure of cells to IL-1 for 15 h prevents this effect. The delay is associated with a lack of cytokine-induced inducible nitric oxide synthase (iNOS) enzyme activity in cell extracts. NIC (20 mM) inhibits NO synthase (NOS) activity in extracts from cells incubated with IL-1 for 6 h and 24 h, and oxyhemoglobin counteracts this inhibition. Hence, NIC could scavenge O2- and allow NO to inhibit the enzyme. The NO donor SIN-1 inhibits in a concentration-dependent manner iNOS activity, and the effect is potentiated by NIC. In intact cells, protection from NIC is associated with IL-1-induced expression of MnSOD activity, and reversible blockade of iNOS expression with pyrrolidine dithiocarbamate counteracts the NIC effect. We conclude that O2- plays a role in preventing NO inhibition of iNOS. The loss of this action coincides with the induction of MnSOD enzyme activity. In addition, the stimulation by NIC of IL-1-induced nitrite production in pyrrolidine dithiocarbamate-treated cells is a novel action that should be considered when the drug is proposed as potential agent for the prevention of insulin-dependent diabetes mellitus.
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PMID:Protection from nicotinamide inhibition of interleukin-1 beta-induced RIN cell nitric oxide formation is associated with induction of MnSOD enzyme activity. 889 50

Previously, we demonstrated apoptotic cell death in the chorion laeve trophoblast layer of human fetal membrane tissues during the late stages of pregnancy, the progression of apoptosis during incubation in vitro, and its suppression by a low concentration of glucocorticoid hormones. We now report examination of mRNA expression of inflammatory cytokines [interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha] and antioxidative enzyme genes [heme oxygenase 1, catalase, Mn-superoxide dismutase (SOD), Cu/Zn-SOD, glutathione S-transferase, glutathione reductase and glutathione peroxidase] and apoptosis-related genes during in vitro progression of apoptosis with or without glucocorticoid by a reverse transcription/PCR method. It was shown that the mRNA levels increased in chorion laeve tissue for each cytokine examined and for catalase, heme oxygenase 1 and Mn-SOD in direct correlation with the in vitro incubation period. By Western blotting the existence of Mn-SOD protein, and its slight increase with incubation time, was also shown. The investigation of the influence of antioxidative reagents [pyrrolidine dithiocarbamate (PDTC), N-acetyl-l-cysteine (NAC) and nordihydroguaiaretic acid (NDGA)] on DNA fragmentation showed that DNA fragmentation in chorion laeve tissues was inhibited by approximately 50% in the presence of 1 mm PDTC, 30 mm NAC and 1 mm NDGA. These results suggest that apoptotic cell death of the trophoblast layer of chorion tissues may be induced through intracellular oxidative stress at the stage of parturition.
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PMID:Progressive apoptosis in chorion laeve trophoblast cells of human fetal membrane tissues during in vitro incubation is suppressed by antioxidative reagents. 1173 13

In the retinoic acid-differentiated neuroblastoma SH-SY5Y cells, IL-1 induced binding activity of NFkappaB and up-regulated the expression and activity of MnSOD. The IL-1-elicited effects were partly reversed by IL-4 and IL-6. It is proposed that IL-4 and IL-6 may participate in the regulation of the imbalanced oxidant status induced by IL-1 in differentiated neuroblastoma cells. In the SH-SY5Y cell line, TNFalpha neither activated NFkappaB nor induced MnSOD expression and activity, but was capable of modulating the IL-1 effects. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NFkappaB activation, down-regulated the expression and activity of MnSOD, which may suggest that the regulation of MnSOD by IL-1 in retinoic acid-differentiated neuroblastoma cells was mediated by the nuclear factor kappaB.
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PMID:Cytokine action and oxidative stress response in differentiated neuroblastoma SH-SY5Y cells. 1451 47