Proteomic Profiles of Thyroid Gland and Gene Expression of the Hypothalamic–Pituitary–Thyroid Axis Are Modulated by Exposure to AgNPs during Prepubertal Rat Stages,Chemical Research in Toxicology

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Proteomic Profiles of Thyroid Gland and Gene Expression of the Hypothalamic–Pituitary–Thyroid Axis Are Modulated by Exposure to AgNPs during Prepubertal Rat Stages
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2020-09-25 , DOI: 10.1021/acs.chemrestox.0c00250
Isabela Medeiros de Oliveira ₁ , Mônica Degraf Cavallin ₁ , Deborah Elzita do Carmo Corrêa ₁ , Amanda Razera ₁ , Danielle Dobner Mariano ₁ , Francine Ferreira ₁ , Marco Aurélio Romano ₁ , Renata Marino Romano ₁

Affiliation

Silver nanoparticles (AgNPs) have potent antimicrobial activity and, for this reason, are incorporated into a variety of products, raising concern about their potential risks and impacts on human health and the environment. The developmental period is highly dependent on thyroid hormones (THs), and puberty is a sensitive period, where changes in the hormonal environment may have permanent effects. We evaluated the hypothalamic–pituitary (HP)–thyroid axis after exposure to low doses of AgNPs using a validated protocol to assess pubertal development and thyroid function in immature male rats. For stimulatory events of the HP–thyroid axis, we observed an increase in the expression of Trh mRNA and serum triiodothyronine. Negative feedback reduced the hypothalamic expression of Dio2 mRNA and increased the expression of Thra1, Thra2, and Thrb2 mRNAs. In the pituitary, there was a reduced expression of Mct-8 mRNA and Dio2 mRNA. For peripheral T3-target tissues, a reduced expression of Mct-8 mRNA was observed in the heart and liver. An increased expression of Dio3 mRNA was observed in the heart and liver, and an increased expression of Thrb2 mRNA was observed in the liver. The quantitative proteomic profile of the thyroid gland indicated a reduction in cytoskeletal proteins (Cap1, Cav1, Lasp1, Marcks, and Tpm4; 1.875 μg AgNP/kg) and a reduction in the profile of chaperones (Hsp90aa1, Hsp90ab1, Hspa8, Hspa9, P4hb) and proteins that participate in the N-glycosylation process (Ddost, Rpn1 and Rpn2) (15 μg AgNP/kg). Exposure to low doses of AgNPs during the window of puberty development affects the regulation of the HP–thyroid axis with further consequences in thyroid gland physiology.

中文翻译：

在青春期前大鼠阶段暴露于 AgNPs 可调节甲状腺的蛋白质组学特征和下丘脑-垂体-甲状腺轴的基因表达

银纳米粒子 (AgNPs) 具有强大的抗菌活性，因此被纳入各种产品中，引起人们对其潜在风险以及对人类健康和环境的影响的担忧。发育期高度依赖甲状腺激素 (THs)，青春期是一个敏感时期，激素环境的变化可能会产生永久性影响。我们使用经过验证的方案评估了暴露于低剂量 AgNPs 后的下丘脑 - 垂体 (HP) - 甲状腺轴，以评估未成熟雄性大鼠的青春期发育和甲状腺功能。对于 HP-甲状腺轴的刺激事件，我们观察到Trh mRNA 和血清三碘甲状腺原氨酸的表达增加。负反馈降低了Dio2的下丘脑表达mRNA 并增加Thra1、Thra2和Thrb2 mRNA 的表达。在垂体中，Mct -8 mRNA 和Dio2 mRNA 的表达降低。对于外周 T3 靶组织，在心脏和肝脏中观察到Mct-8 mRNA 的表达降低。的表达增加DIO3在心脏和肝脏中观察到的mRNA，和的表达增加Thrb2在肝脏中观察到mRNA。甲状腺的定量蛋白质组学特征表明细胞骨架蛋白（Cap1、Cav1、Lasp1、Marcks 和 Tpm4；1.875 μg AgNP/kg）的减少和伴侣蛋白（Hsp90aa1、Hsp90ab1、Hspa8、Hspa9、P4b）的减少) 和参与 N-糖基化过程的蛋白质 (Ddost、Rpn1 和 Rpn2) (15 μg AgNP/kg)。在青春期发育窗口期间接触低剂量的 AgNPs 会影响 HP-甲状腺轴的调节，从而进一步影响甲状腺生理学。

更新日期：2020-10-21

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