相思豆毒素中毒小鼠分子毒理的肝脏蛋白质组学研究

Proteomics Analysis of Abrin Toxicity in Mouse Liver

目的利用蛋白质组学技术研究相思豆毒素中毒小鼠肝脏差异表达蛋白。方法采用二维凝胶电泳分离肝脏蛋白样品,以飞行时间质谱、生物信息学分析等方法鉴定各差异表达蛋白。结果小鼠相思豆毒素中毒后共鉴定出11个明显变化的肝脏差异表达蛋白,其中6个蛋白表达明显上调,分别为半胱氨酸蛋白酶-3、G-蛋白β亚基、乙酰辅酶A脱氢酶、胞浆天冬氨酸氨基转移酶、核转录因子抑制剂IKK-A及p53-结合蛋白Mdm4;表达明显下调的5个蛋白分别是H+-三磷酸腺苷(H+-ATP)合酶、微粒体核糖体蛋白L39、细胞核酸结合样蛋白、成纤维细胞生长因子-12及硫代硫酸硫转移酶。结论小鼠相思豆毒素中毒后,发生变化的肝脏蛋白多数为具有凋亡诱导、能量代谢、增殖和分化等作用的功能性蛋白,其分子毒理涉及复杂的网络信号传导机制。

Objective To identify the hepatic protein targets involved in abrin toxicity in mice. Methods Two- dimensional gel electrophoresis and mass spectrometry were used. Results Proteomics and bioinformatics analysis showed that 11 proteins were significantly affected in mice treated with abrin. Among the 11 proteins, G- protein beta subunit, aspartate aminotransferase, IKK- A, Caspase- 3 and p53- binding protein Mdm4 were all upregulated, while mitochondrial ribosomal protein L39, cellular nucleic acid binding- like protein, fibroblast growth factor- 12, thiosulfate sulfurtransferase and H^＋ - transporting ATP synthase were downregulated. Conclusion The differentially expressed protein are functional proteins involved in proliferation and differentiation, apoptosis, energy metabolism and antioxidation, These results demonstrate that abrin induced toxicity is a multistep process containing different molecular mechanisms in vivo.