The role of HO-1 in protection against lead-induced neurotoxicity
The role of HO-1 in protection against lead-induced neurotoxicity
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DOI：
10.1016/j.neuro.2015.10.015
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发表时间：
2016-01-01
期刊：
影响因子：
3.4
通讯作者：
Chen, Jun
中科院分区：
文献类型：
--
作者：
Li, Xiaoyi;Ye, Fang;Chen, Jun
铅是一种普遍存在的持久性环境污染物，对所有生物体产生有害影响，并继续威胁全球范围内的公众健康。血红素加氧酶-1（HO-1）是一种应激诱导酶，介导抗氧化和细胞保护作用，以维持细胞氧化还原稳态，保护细胞免受氧化应激。本研究旨在探讨HO-1在铅神经毒性保护中的作用及其信号通路。醋酸铅（PbAc）暴露可导致原代大鼠海马神经元和SH-SY 5 Y细胞HO-1表达增加。PbAc诱导的细胞内活性氧（ROS）也增加，细胞活力下降的SH-SY 5 Y细胞。我们进一步证明了PbAc可以通过ROS依赖性的P38、ERK 1/2和PI 3 K/AKT信号通路和非ROS依赖性的JNK信号通路诱导HO-1的表达。进一步研究发现HO-1过表达可显著抑制PbAc诱导的SH-SY 5 Y细胞凋亡和ROS的产生。此外，HO-1基因敲低加重PbAc诱导的细胞凋亡和ROS的产生。本研究结果表明HO-1是一种新型的保护因子，能够有效抑制PbAc诱导的神经系统氧化应激和细胞死亡，从而为铅相关疾病的预防和治疗提供潜在的治疗策略。(C)2015爱思唯尔公司All rights reserved.
Lead is a pervasive and persistent environmental pollutant that exerts deleterious effects on all living organisms and continues to threaten public health on a global scale. Heme oxygenase-1 (HO-1) is a stress-inducible enzyme that mediates antioxidative and cytoprotective effects to maintain cellular redox homeostasis and protect cells from oxidative stress. This study was designed to explore the role of HO-1 in protection against lead neurotoxicity and the signaling pathways involved. Lead acetate (PbAc) exposure resulted in increased HO-1 expression in primary rat hippocampal neurons and SH-SY5Y cells. PbAc-induced intracellular reactive oxygen species (ROS) also increased, and cell viability decreased in SH-SY5Y cells. We further demonstrated that HO-1 could be induced by PbAc through the P38, ERK1/2, and PI3K/AKT signaling pathways in a ROS-dependent manner and through the JNK pathway in a ROS-independent manner. Further investigation revealed that HO-1 overexpression significantly restrained cell apoptosis and ROS production induced by PbAc in SH-SY5Y cells. Moreover, HO-1 knockdown aggravated PbAc-induced cell apoptosis and ROS production. Our results indicated that HO-1 was a novel protective factor that could efficiently inhibit PbAc-induced oxidative stress and cell death in the nervous system, thereby providing the potential therapeutic strategies for the prevention and treatment of lead-related diseases. (C) 2015 Elsevier Inc. All rights reserved.