Effects of persistent organochlorine exposure on the liver transcriptome of the common minke whale (Balaenoptera acutorostrata) from the North Pacific.
Effects of persistent organochlorine exposure on the liver transcriptome of the common minke whale (Balaenoptera acutorostrata) from the North Pacific.
复制标题
持续接触有机氯对北太平洋小须鲸（Balaenoptera acutorostrata）肝脏转录组的影响。
DOI：
10.1016/j.ecoenv.2014.06.028
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发表时间：
2014
影响因子：
6.8
通讯作者：
H.
中科院分区：
文献类型：
--
作者：
Niimi;S.;Imoto;M.;Kunisue;T.;Watanabe;M.X.;Kim;E.Y.;Nakayama;K.;Yasunaga;G.;Fujise;Y.;Tanabe;S.;Iwata;H.
测定了北太平洋小须鲸（Balaenoptera acutorostrata）肝脏中持久性有机氯（OCs）的浓度。为了研究OC对小须鲸转录组的影响，本研究构建了该物种的肝脏寡核苷酸阵列，其中点样了985个独特的寡核苷酸，并进一步分析了OC水平与肝脏组织基因表达谱之间的关系。逐步多元线性回归分析确定了32个与肝脏OC水平相关的基因。7个细胞色素P450（CYP1A1，1A2，2C78，2E1，3A72，4A35和4V6）基因的mRNA表达水平与每种OC的浓度没有明显的相关性，表明肝脏中积累的OC没有达到可以改变CYP450表达的水平。在通过定制寡核苷酸阵列分析筛选的基因中，使用定量实时逆转录聚合酶链反应进一步测量16个基因的肝脏mRNA表达水平。维生素D结合蛋白（DBP）mRNA水平与非共面多氯联苯（PCB）水平呈负相关。雄激素受体相关辅调节子70（ARA 70）的表达水平与非正交共面PCB169的浓度呈显著正相关。这些相关性表明，共面PCB减少DBP的表达可以抑制维生素D受体介导的信号级联在外周组织。或者，维生素D受体信号级联的抑制可以通过与雄激素受体信号通路竞争ARA 70来增强。此外，还观察到犬尿氨酸酶和PCB169水平之间的负相关性，这表明内源性芳烃受体激动剂犬尿氨酸在小须鲸种群中的积累增加。需要进一步研究将转录组的变化转化为毒理学结果，包括神经和免疫系统的破坏。
Hepatic concentrations of persistent organochlorines (OCs) were determined in the common minke whale (Balaenoptera acutorostrata) from the North Pacific. To investigate the effects of OCs on the transcriptome in the minke whale, the present study constructed a hepatic oligo array of this species where 985 unique oligonucleotides were spotted and further analyzed the relationship between the OC levels and gene expression profiles of liver tissues. The stepwise multiple linear regression analysis identified 32 genes that correlated with hepatic OC levels. The mRNA expression levels of seven cytochrome P450 (CYP) genes,CYP1A1, 1A2, 2C78, 2E1, 3A72, 4A35, and 4V6 showed no clear correlations with the concentration of each OC, suggesting that the accumulated OCs in the liver did not reach levels that could alter CYP expression. Among the genes screened by the custom oligo array analysis, hepatic mRNA expression levels of 16 genes were further measured using quantitative real-time reverse transcription polymerase chain reaction. The mRNA levels of vitamin D-binding protein (DBP) were negatively correlated with non-orthocoplanar polychlorinated biphenyl (PCB) levels. Androgen receptor-associated coregulator 70 (ARA70) expression levels showed a significant positive correlation with concentrations of non-orthocoplanar PCB169. These correlations suggest that coplanar PCB-reduced DBP expression could suppress vitamin D receptor-mediated signaling cascades in peripheral tissues. Alternatively, the suppression of vitamin D receptor signaling cascade could be enhanced through competition with the androgen receptor signaling pathway for ARA70. In addition, a negative correlation between kynureninase and PCB169 levels was also observed, which suggest an enhanced accumulation of an endogenous aryl hydrocarbon receptor agonist, kynurenine in the minke whale population. Further studies are necessary to translate the changes in the transcriptome to toxicological outcomes including the disruption of the nervous and immune systems.