首页> 外文期刊>Journal of biochemical and molecular toxicology >Molecular characterization and expression of arginine vasotocin Vla2 receptor in Atlantic croaker brain: Potential mechanisms of its downregulation by PCB77
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Molecular characterization and expression of arginine vasotocin Vla2 receptor in Atlantic croaker brain: Potential mechanisms of its downregulation by PCB77

机译:大西洋叉箱脑中精氨酸血管谱VLA2受体的分子表征及表达:PCB77下调其下调的潜在机制

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The arginine vasotocin (AVT)-V1a receptor mediates critical reproductive behaviors of the nonapeptide vasotocin in the teleost brain. In this study, we report the molecular characterization of the AVT-V1a2 receptor and its messenger RNA (mRNA) and protein expressions in the Atlantic croaker brain after exposure to the planar polychlorinated biphenyl congener 3,3',4,4'-tetrachlorobiphenyl (PCB77). The full-length sequence of croaker AVT-V1a2 receptor complementary DNA (cDNA) is highly homologous to other teleost AVT-V1a2 receptor cDNAs. Double-labeled immunohistochemistry showed coexpression of AVT-V1a2 receptor and gonadotropin-releasing hormone-l (GnRH-l, a neuropeptide that regulates gonado-tropin secretion) in hypothalamic neurons, thereby providing the anatomical basis for possible AVT modulation of croaker reproduction through alterations in GnRH-l secretion. AVT-V1a2 receptor mRNA and protein levels as well as GnRH-l mRNA levels were markedly decreased in hypothalamic tissues of croaker exposed to PCB77 (dose: 2 and 8μg/g body weight for 4 weeks) compared with levels in untreated (control) fish. In contrast, hypothalamic cytochrome P450 1A (CYP1A, a monooxygenase enzyme) and interleukin-1β (IL-1β, a cytokine indicator of inflammation and response to neuronal damage) mRNA levels, and plasma protein carbonyl (PC, an indicator of reactive oxygen species) contents, important biomarkers of neural stress, were increased in PCB77-exposed fish compared with controls. Collectively, these results suggest that the downregulation of hypothalamic AVT-V1a2 receptor and GnRH-l transcripts due to PCB77 exposure is associated with induction of CYP1A, cellular inflammation and oxidative stress in Atlantic croaker, a marine teleost that inhabits estuaries along the US Atlantic coast and the Gulf of Mexico that are often contaminated with persistent organic pollutants such as PCBs.
机译:精氨酸血管催产素(AVT)-V1a受体介导硬骨鱼类大脑中九肽血管催产素的关键生殖行为。在这项研究中,我们报告了暴露于平面多氯联苯同系物3,3',4,4'-四氯联苯(PCB77)后大西洋黄鱼脑中AVT-V1a2受体及其信使RNA(mRNA)和蛋白质表达的分子特征。黄鱼AVT-V1a2受体互补DNA(cDNA)的全长序列与其他硬骨鱼AVT-V1a2受体cDNA高度同源。双标免疫组织化学显示AVT-V1a2受体和促性腺激素释放激素-l(GnRH-l,一种调节促性腺激素分泌的神经肽)在下丘脑神经元中共表达,从而为AVT通过GnRH-l分泌的改变调节黄鱼繁殖提供了解剖学基础。与未经处理(对照)的鱼相比,暴露于PCB77(剂量:2和8μg/g体重,持续4周)的大黄鱼下丘脑组织中的AVT-V1a2受体mRNA和蛋白质水平以及GnRH-l mRNA水平显著降低。相比之下,与对照组相比,接触PCB77的鱼类下丘脑细胞色素P450 1A(CYP1A,一种单加氧酶)和白细胞介素-1β(IL-1β,一种炎症和神经元损伤反应的细胞因子指示剂)mRNA水平以及血浆蛋白羰基(PC,一种活性氧物种指示剂)含量增加,这是神经应激的重要生物标记物。总之,这些结果表明,PCB77暴露导致下丘脑AVT-V1a2受体和GnRH-l转录物的下调与CYP1A的诱导、细胞炎症和氧化应激有关,一种海洋硬骨鱼,栖息于美国大西洋海岸和墨西哥湾沿岸的河口,经常受到持久性有机污染物(如多氯联苯)的污染。

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