Borrello S, De Leo M E, Landriscina M, Palazzotti B, Galeotti T
Institute of General Pathology, Catholic University, Rome, Italy.
Biochem Biophys Res Commun. 1996 Mar 27;220(3):546-52. doi: 10.1006/bbrc.1996.0441.
In vivo experiments demonstrate that rat liver manganese-containing superoxide dismutase (MnSOD) is up-regulated at the transcriptional level following the inactivation of copper-zinc superoxide dismutase (CuZnSOD). CuZnSOD activity was inhibited by the administration of the copper chelating agent diethyldithiocarbamate (DDC). This CuZnSOD inactivation is likely associated with an intracellular oxidative stress. Indeed the antioxidant N-acetyl-cysteine (NAC) completely prevents the MnSOD mRNA up-regulation observed after DDC administration. Evidence is also provided that an approximately 50% diminution of the total iron content in the tissue, which follows the in vivo administration of the iron chelator desferrioxamine (DESF), reduces the amount of MnSOD induction achieved by DDC treatment. Both NAC and DESF significantly down-regulate MnSOD gene expression also in normal untreated rat liver. While the observed inhibitory effect of NAC in MnSOD mRNA up-regulation can be ascribed mainly to its antioxidant property, iron chelation could act with an antioxidant effect and/or affecting some iron-dependent factor(s) possibly involved in MnSOD gene regulation. It is proposed that this metal could have a role among factors that sense and/or trigger transcription of the MnSOD gene.
体内实验表明，在铜锌超氧化物歧化酶（CuZnSOD）失活后，大鼠肝脏含锰超氧化物歧化酶（MnSOD）在转录水平上被上调。通过给予铜螯合剂二乙基二硫代氨基甲酸盐（DDC）抑制CuZnSOD活性。这种CuZnSOD失活可能与细胞内氧化应激有关。实际上，抗氧化剂N-乙酰半胱氨酸（NAC）完全阻止了DDC给药后观察到的MnSOD mRNA上调。还提供了证据表明，体内给予铁螯合剂去铁胺（DESF）后，组织中铁总含量约减少50%，降低了DDC处理所实现的MnSOD诱导量。NAC和DESF在正常未处理的大鼠肝脏中也显著下调MnSOD基因表达。虽然观察到的NAC对MnSOD mRNA上调的抑制作用主要可归因于其抗氧化特性，但铁螯合可能通过抗氧化作用和/或影响一些可能参与MnSOD基因调控的铁依赖性因子而起作用。有人提出，这种金属可能在感知和/或触发MnSOD基因转录的因素中起作用。
