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首页> 外文期刊>Cellular Physiology and Biochemistry >Ligand-independent tyrosine kinase signalling in RTH 149 trout hepatoma cells: Comparison among heavy metals and pro-oxidants
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Ligand-independent tyrosine kinase signalling in RTH 149 trout hepatoma cells: Comparison among heavy metals and pro-oxidants

机译：RTH 149鳟鱼肝癌细胞中不依赖配体的酪氨酸激酶信号转导：重金属和促氧化剂之间的比较

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Tyrosine phosphorylation depends on the activity of receptor and non-receptor tyrosine kinases and promote cell growth, differentiation and apoptosis. Different stressors are known to stimulate tyrosine kinase activities and this could explain a wide spectrum of effects that these agents produce on different organisms. We studied the effects of heavy metals and pro-oxidants on tyrosine kinase signalling in trout hepatoma cells (RTH 149) by Western immunoblotting. Use of antiphosphotyrosine showed that Hg2+ and Cu2+ in the muM range, and H2O2 in the mM range, induced tyrosine phosphorylation. The effect Of Cu2+ was prevented by pre-incubation with genistein, while those of Hg2+ and H2O2 were only decreased, probably due to tyrosine kinase stimulation coupled to phosphatase inhibition. Phosphospecific antibodies against the three types of MAPKs showed that ERK is activated by heavy metals only, while p38 and SAPK/JNK are activated by H2O2, Hg2+, and Cu2+ plus low H2O2. Cell pre-incubation with p38 inhibitors indicated that ERK activation by H2O2 is prevented by concomitant activation of p38. Phosphospecific STAT antibodies revealed activation by H2O2 only. In conclusion, fish cell exposure to heavy metals and pro-oxidants produce specific tyrosine kinase responses, involving cross talk and redox modulatory effects. Copyright (C) 2003 S. Karger AG, Basel. [References: 50]
机译：酪氨酸磷酸化取决于受体和非受体酪氨酸激酶的活性并促进细胞生长，分化和凋亡。已知不同的应激源会刺激酪氨酸激酶的活性，这可以解释这些因子对不同生物体产生的广泛影响。我们通过Western免疫印迹研究了重金属和前氧化剂对鳟鱼肝癌细胞（RTH 149）中酪氨酸激酶信号转导的影响。使用抗磷酸酪氨酸表明，在muM范围内的Hg2 +和Cu2 +和在mM范围内的H2O2诱导了酪氨酸磷酸化。通过与染料木黄酮的预温育可防止Cu2 +的作用，而仅降低Hg2 +和H2O2的作用，这可能是由于酪氨酸激酶刺激和磷酸酶抑制作用所致。针对这三种类型的MAPK的磷酸化特异性抗体显示ERK仅被重金属激活，而p38和SAPK / JNK被H2O2，Hg2 +和Cu2 +加低H2O2激活。用p38抑制剂预孵育细胞表明，伴随着p38的激活可以阻止H2O2激活ERK。磷酸化的STAT抗体显示仅被H2O2激活。总之，鱼细胞暴露于重金属和促氧化剂会产生特定的酪氨酸激酶反应，涉及串扰和氧化还原调节作用。版权所有（C）2003 S.Karger AG，巴塞尔。 [参考：50]

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