Matsumoto Takuya, Feroudj Holger, Kikuchi Ryosuke, Kawana Yuriko, Kondo Hidehiro, Hirono Ikuo, Mochizuki Toshiaki, Nagashima Yuji, Kaneko Gen, Ushio Hideki, Kodama Masaaki, Watabe Shugo
Department of Aquatic Bioscience, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo, Tokyo 113-8657, Japan.
Laboratory of Genome Science, Graduate School of Marine Science and Technology, Tokyo University of Marine Science and Technology, Minato, Tokyo 108-8477, Japan.
Microarrays (Basel). 2014 Oct 27;3(4):226-44. doi: 10.3390/microarrays3040226.
Pufferfish accumulate tetrodotoxin (TTX) mainly in the liver and ovary. This study aims at investigating the effect of TTX accumulation in the liver of cultured specimens of torafugu Takifugu rubripes on the hepatic gene expression by microarray analysis on Day 5 after the intramuscular administration of 0.25 mg TTX/kg body weight into the caudal muscle. TTX was detected in the liver, skin and ovary in the TTX-administered individuals. The total amount of TTX accumulated in the body was 67 ± 8% of the administered dose on Day 5. Compared with the buffer-administered control group, a total of 59 genes were significantly upregulated more than two-fold in the TTX-administered group, including those encoding chymotrypsin-like elastase family member 2A, transmembrane protein 168 and Rho GTP-activating protein 29. In contrast, a total of 427 genes were downregulated by TTX administration, including those encoding elongation factor G2, R-spondin-3, nuclear receptor activator 2 and fatty acyl-CoA hydrolase precursor. In conclusion, our results demonstrate that the intramuscular administration of TTX changes the expression of hepatic genes involved in various signaling pathways.
河豚主要在肝脏和卵巢中积累河豚毒素(TTX)。本研究旨在通过对养殖红鳍东方鲀肌肉注射0.25毫克TTX/千克体重5天后进行基因芯片分析,研究肝脏中TTX积累对肝脏基因表达的影响。在注射TTX的个体的肝脏、皮肤和卵巢中检测到了TTX。在第5天,体内积累的TTX总量为给药剂量的67±8%。与注射缓冲液的对照组相比,在注射TTX的组中共有59个基因显著上调两倍以上,包括编码类胰凝乳蛋白酶样弹性蛋白酶家族成员2A、跨膜蛋白168和Rho GTP激活蛋白29的基因。相反,共有427个基因因TTX给药而下调,包括编码延伸因子G2、R-脊椎蛋白-3、核受体激活剂2和脂肪酰辅酶A水解酶前体的基因。总之,我们的结果表明,肌肉注射TTX会改变参与各种信号通路的肝脏基因的表达。