The effect of lead exposure on expression of SIRT1 in the rat hippocampus
The effect of lead exposure on expression of SIRT1 in the rat hippocampus
复制标题
铅暴露对大鼠海马SIRT1表达的影响
DOI：
10.1016/j.etap.2016.04.008
复制
发表时间：
2016-06-01
影响因子：
4.3
通讯作者：
Fan, Guangqin
中科院分区：
文献类型：
--
作者：
Feng, Chang;Gu, Junwang;Fan, Guangqin
基于沉默信息调节器2同源物1（SIRT1）如何调节环AMP反应元件结合蛋白（CREB）（维持认知功能的长期记忆的分子开关），推测铅（Pb）对SIRT1的影响是导致Pb诱导的认知和学习缺陷的机制之一。因此，本研究的目的是研究 Pb 暴露对 SIRT1 表达的影响，以及 SIRT1 激活剂白藜芦醇的逆转作用。我们研究了母鼠在妊娠和哺乳期间摄入饮用水中的 Pb 对产后第 3 周（PNW3）和第 52 周（PNW52）后代海马 SIRT1 和 CREB 表达的影响，然后在灌胃白藜芦醇 4 周后重新检查这些对后代的影响。 Pb 暴露以剂量依赖性方式降低 PNW3 和 52 大鼠海马中 SIRT1 和 CREB 磷酸化，而白藜芦醇逆转了这些损失。这些结果表明 SIRT1 可能是预防 Pb 神经毒性的新靶点。 (C) 2016 Elsevier B.V. 保留所有权利。
Based on how the silent information regulator 2 homolog 1 (SIRT1) regulates the cyclic AMP response element binding protein (CREB), which is the molecular switch of long-term memory that maintains cognitive function, it is postulated that the impact of lead (Pb) on SIRT1 is one of the mechanisms leading to Pb-induced cognitive and learning deficits. Hence, the purpose of this study was to investigate the effect of Pb exposure on the expression of SIRT1, and the reversion effect of resveratrol, which is an activator of SIRT1. We examined the effects of maternal rat ingestion of Pb in drinking water during gestation and lactation on the expression of SIRT1 and CREB in the hippocampus of their offspring at postnatal week 3 (PNW3) and 52 (PNW52), and then reexamined these effects in offspring after intragastric administration of resveratrol for 4 weeks. Pb exposure decreased SIRT1 and CREB phosphorylation in a dose-dependent manner in the rat hippocampus at both PNW3 and 52, and resveratrol reversed those losses. These results indicated that SIRT1 might be a novel target to prevent Pb neurotoxicity. (C) 2016 Elsevier B.V. All rights reserved.