胞内SOD1活性的ATSM抑制对ERK信号通路的影响

ATSM inhibition of intracellular SOD1 activity and its effect on ERK signaling pathway

铜锌超氧化物歧化酶(SOD1)是胞内分布最广的最重要的抗氧化酶之一,其功能是催化超氧阴离子(O??2)歧化为过氧化氢(H2O2),维持胞内O??2和H2O2的内稳态浓度.高浓度的H2O2通过可逆氧化修饰信号蛋白(如磷酸酶)活性部位的半胱氨酸残基,导致胞内活性氧(ROS)信号通路异常.以对Cu2+有高亲和力的ATSM为螯合剂,夺取SOD1活性部位中的铜,使其失活.在不影响细胞内SOD1表达的情况下,ATSM有效抑制了SOD1的活性,改变了胞内O??2和H2O2的相对浓度,降低了MAPK信号通路中ERK的磷酸化水平.

Cu/Zn superoxide dismutase（SOD1）, one of the most important and widely distributed antioxidant enzymes, maintains the homeostasis of intracellular superoxide anion（O？？2） and peroxide hydrogen（H2O2） by catalyzing the dismutation of superoxide to peroxide hydrogen. When at high levels, H2O2 can inactivate signaling proteins by reversibly oxidazing their cysteine residues at active sites, resulting in an aberrant redox signaling network. Diacetylbis-N（4）-methylthiosemicarbazonat（ATSM）, acting as a chelating agent for cooper with high affinity, is available for inactivating SOD1 by chelating the copper from the active site. It can effectively inhibited the activity of SOD1 without affecting its expression, thereby changing the intracellular concentrations of O？？2 and peroxide hydrogen, which finally leading to the decreasing of ERK phosphorylation in the relative signaling pathways.