Proteomic characterization of the effects of clofibrate on protein expression in rat liver
Proteomic characterization of the effects of clofibrate on protein expression in rat liver
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DOI：
10.1002/pmic.200500251
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发表时间：
2006-03-01
期刊：
影响因子：
3.4
通讯作者：
Gautier, JC
中科院分区：
文献类型：
--
作者：
Léonard, JF;Courcol, M;Gautier, JC
氯贝特是一种过氧化物酶体增殖剂，已知可诱导大鼠肝脏肿瘤。一项蛋白质组学研究为氯贝特诱导的非基因毒性肝癌发生的分子机制提供了新的见解。大鼠口服氯贝特250 mg/kg d， 7 d后处死。采用DIGE技术对肝脏中提取的蛋白质进行2-DE分析。质谱鉴定表明，clofibrate诱导77个蛋白表达上调，27个蛋白表达下调。最高表达率对应于脂质代谢、脂肪酸代谢、氨基酸代谢、蛋白质代谢、柠檬酸循环、外源解毒和氧化应激等一系列生化途径的蛋白质。与细胞增殖和凋亡有关的蛋白质，如禁止蛋白、10-甲酰基四氢叶酸脱氢酶、衰老标记蛋白-30、吡哆醇5'-磷酸氧化酶和vimentin，也被确定为受到调节。这些结果为进一步研究氯贝特诱导肝脏肿瘤的分子机制提供了线索。此外，MS结果显示，在不同pI和/或M-r对应的几个点上检测到一系列调节蛋白。这些变异的差异效应可能是由特异性PTM引起的，可能是氯贝酸盐诱导的大鼠肝脏蛋白质表达调节的特定分子特征。
Clofibrate is a peroxisome proliferator known to induce liver tumours in rats. A proteomics study was conducted to provide new insights into the molecular mechanisms of clofibrate-induced non-genotoxic hepatocarcinogenesis. Rats were treated with 250 mg/kg day clofibrate orally and sacrificed after 7 days. Proteins extracted from the liver were analysed by 2-DE using DIGE technology. The protein identification performed by MS showed that clofibrate induced up-regulation of 77 proteins and down-regulation of 27 proteins. The highest expression ratios corresponded to proteins involved in a series of biochemical pathways such as lipid metabolism, fatty acid metabolism, amino acid metabolism, protein metabolism, citric acid cycle, xenobiotic detoxification and oxidative stress. Proteins implicated in cell proliferation and apoptosis, such as prohibitin, 10-formyl tetrahydrofolate dehydrogenase, senescence marker protein-30, pyridoxine 5'-phosphate oxidase and vimentin, were also identified as being regulated. These results provide leads for further investigations into the molecular mechanisms of liver tumours induced by clofibrate. In addition, MS results showed that a series of regulated proteins were detected as several spots corresponding to different pI and/or M-r. Differential effects on those variants could result from specific PTM and could be a specific molecular signature of the clofibrate-induced protein expression modulation in rat liver.