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

Nitric oxide (NO) released from (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1- ium-1,2-diolate (DETA/NO or NOC-18) induces apoptosis in human leukemia HL-60 cells. In this study, we isolated a HL-60 variant cell line, HL-NR6, that is resistant to DETA/NO toxicity as assessed by DNA fragmentation, morphology, and colony forming ability. The variant cells also showed resistance to reactive oxygen species (ROS) such as superoxide and hydrogen peroxide as well as NO donors, but not to anti-tumor drugs. We found that HL-NR6 cells when compared with HL-60 cells possessed twice the activities of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and catalase, but no change in Mn-SOD nor in glutathione peroxidase. Immunoblotting confirmed the high levels of both enzymes in the variant cell. We also observed that ROS generation following DETA/NO exposure was substantially higher in HL-60 cells than in HL-NR6 cells, using the 2',7'-dichlorofluorescein fluorometric method. Moreover, the SOD mimetic Mn(III) tetrakis(1-methyl-4-pyridyl) porphyrin and exogenous catalase effectively attenuated DETA/NO-elicited DNA fragmentation in HL-60 cells. Taken together, these data suggested that the NO resistance in HL-NR6 cells is associated with the increased Cu,Zn-SOD/catalase and that NO-mediated apoptosis in HL-60 cells is correlated with the generation of ROS and derived molecules like peroxynitrite.
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PMID:Resistance to nitric oxide-mediated apoptosis in HL-60 variant cells is associated with increased activities of Cu,Zn-superoxide dismutase and catalase. 989 23

The effect of Cu plate on the cellular function was investigated by two different methods: an extraction method (Method I) and a direct contact method (Method II). In Method I, the supernatant of the culture medium, which had been pre-incubated with Cu plate, was added to mouse macrophage-like Raw 264.7 cells. This supernatant dose-dependently inhibited the proliferation and nitric oxide (NO) production by lipopolysaccharide-stimulated Raw 264.7 cells. In Method II, human promyelocytic leukemic HL-60 cells in suspension were incubated with culture medium which contained Cu plate. The direct contact with Cu plate rapidly suppressed the proliferation and MnSOD and Cu/ZnSOD activities. The suppressed proliferation and SOD activity reverted to or exceeded the control level by sodium ascorbate, whereas N-acetyl-L-cysteine (NAC) only reactivated the proliferation, but not the SOD activity. ESR spectroscopy showed that contact with Cu plate slightly diminished the hydroxyl radical (generated by Fenton reaction), without affecting the intensity of NO (produced from NOC-7) and DPPH radical. The present study suggests that two representative antioxidants, such as sodium ascorbate and NAC, protect the cells from Cu-induced cytotoxicity via different mechanisms.
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PMID:Protection by antioxidants of copper-induced decline of proliferation and SOD activity. 1581 49