Thongphasuk J, Oberley L W, Oberley T D
B180 Medical Laboratories, University of Iowa, Iowa City, Iowa, 52242, USA.
Arch Biochem Biophys. 1999 May 15;365(2):317-27. doi: 10.1006/abbi.1999.1179.
MnCl2 induced manganese-containing superoxide dismutase (MnSOD) expression (mRNA, immunoreactive protein, and enzyme activity) in human breast cancer Hs578T cells. The induction of MnSOD immunoreactive protein in Hs578T cells was inhibited by tiron (a metal chelator and superoxide scavenger), pyruvate (a hydrogen peroxide scavenger), or 2-deoxy-d-glucose (DG, an inhibitor of glycolysis and the hexose monophosphate shunt), but not by 5,5-dimethyl-1-pyrroline-1-oxide (a superoxide scavenger), N-acetyl cysteine (a scavenger for reactive oxygen species and precursor of glutathione), diphenylene iodonium (an inhibitor of flavoproteins such as NADPH oxidase and nitric oxide synthase), or SOD (a superoxide scavenger). Northern blotting demonstrated that tiron or DG affected at the mRNA level, while pyruvate affected Mn-induced MnSOD expression at both the mRNA and protein levels. These results demonstrate that Mn can induce MnSOD expression in cultured human breast cancer cells. Mn also induced apoptosis and necrosis in these cells. Since inhibitors of Mn-induced MnSOD induction did not affect cell viability, MnSOD induction is probably not the cause of the Mn-induced cell killing.
氯化锰可诱导人乳腺癌Hs578T细胞中含锰超氧化物歧化酶（MnSOD）的表达（mRNA、免疫反应性蛋白和酶活性）。在Hs578T细胞中，MnSOD免疫反应性蛋白的诱导受到替络龙（一种金属螯合剂和超氧化物清除剂）、丙酮酸（一种过氧化氢清除剂）或2-脱氧-D-葡萄糖（DG，一种糖酵解和磷酸己糖旁路抑制剂）的抑制，但不受5,5-二甲基-1-吡咯啉-N-氧化物（一种超氧化物清除剂）、N-乙酰半胱氨酸（一种活性氧清除剂和谷胱甘肽前体）、二苯碘鎓（一种黄素蛋白如NADPH氧化酶和一氧化氮合酶的抑制剂）或超氧化物歧化酶（一种超氧化物清除剂）的抑制。Northern印迹法表明，替络龙或DG在mRNA水平上产生影响，而丙酮酸在mRNA和蛋白水平上均影响锰诱导的MnSOD表达。这些结果表明，锰可诱导培养的人乳腺癌细胞中MnSOD的表达。锰还可诱导这些细胞凋亡和坏死。由于锰诱导的MnSOD诱导抑制剂不影响细胞活力，因此MnSOD诱导可能不是锰诱导细胞杀伤的原因。
