Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues
Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues
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DOI：
10.1152/ajpcell.00529.2009
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发表时间：
2010-10-01
影响因子：
5.5
通讯作者：
Zhang, Kezhong
中科院分区：
文献类型：
--
作者：
Laing, Suzette;Wang, Guohui;Zhang, Kezhong
Laing S，Wang G，Briazova T，Zhang C，Wang A，Zheng Z，Gow A，Chen AF，Rajagopalan S，Chen LC，Sun Q，Zhang K。空气中的颗粒物选择性激活肺和肝组织中的内质网应激反应。 Am J Physiol Cell Physiol 299: C736-C749, 2010. First published June 16, 2010; doi:10.1152/ajpcell.00529.2009.-最近的研究表明，吸入颗粒物 (PM) 暴露与肺部和心血管疾病相关的死亡率和发病率增加之间存在联系。 However, a precise understanding of the biological mechanism underlying PM-associated toxicity and pathogenesis remains elusive. Here, we investigated the impact of PM exposure in intracellular stress signaling pathways with animal models and cultured cells.小鼠吸入暴露于环境相关的细颗粒物（空气动力学直径 < 2.5 μm，PM2.5）会诱导肺和肝组织以及小鼠巨噬细胞系 RAW264.7 中的内质网 (ER) 应激和未折叠蛋白反应 (UPR) 的激活。环境 PM2.5 暴露会激活双链 RNA 激活蛋白激酶样 ER 激酶 (PERK)，导致翻译起始因子 eIF2 α 磷酸化并诱导 C/EBP 同源转录因子 CHOP/GADD153。 Activation of PERK-mediated UPR pathway relies on the production of reactive oxygen species (ROS) and is critical for PM2.5-induced apoptosis.此外，PM2.5 暴露可以激活 ER 应激传感器 IRE1 α，但会降低 IRE1 α 在剪接编码 UPR 反式激活剂 X-box 结合蛋白 1 (XBP1) 的 mRNA 方面的活性。总之，我们的研究表明，PM2.5 暴露会差异性地激活 UPR 分支，从而通过 PERK-eIF2 α-CHOP UPR 分支导致 ER 应激诱导的细胞凋亡。这项工作提供了关于环境 PM2.5 暴露引发细胞毒性作用的细胞和分子基础的新见解，这种作用可能与空气污染相关的发病机制有关。
Laing S, Wang G, Briazova T, Zhang C, Wang A, Zheng Z, Gow A, Chen AF, Rajagopalan S, Chen LC, Sun Q, Zhang K. Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues. Am J Physiol Cell Physiol 299: C736-C749, 2010. First published June 16, 2010; doi:10.1152/ajpcell.00529.2009.-Recent studies have suggested a link between inhaled particulate matter (PM) exposure and increased mortality and morbidity associated with pulmonary and cardiovascular diseases. However, a precise understanding of the biological mechanism underlying PM-associated toxicity and pathogenesis remains elusive. Here, we investigated the impact of PM exposure in intracellular stress signaling pathways with animal models and cultured cells. Inhalation exposure of the mice to environmentally relevant fine particulate matter (aerodynamic diameter < 2.5 mu m, PM2.5) induces endoplasmic reticulum (ER) stress and activation of unfolded protein response (UPR) in the lung and liver tissues as well as in the mouse macrophage cell line RAW264.7. Ambient PM2.5 exposure activates double-strand RNA-activated protein kinase-like ER kinase (PERK), leading to phosphorylation of translation initiation factor eIF2 alpha and induction of C/EBP homologous transcription factor CHOP/GADD153. Activation of PERK-mediated UPR pathway relies on the production of reactive oxygen species (ROS) and is critical for PM2.5-induced apoptosis. Furthermore, PM2.5 exposure can activate ER stress sensor IRE1 alpha, but it decreases the activity of IRE1 alpha in splicing the mRNA encoding the UPR trans-activator X-box binding protein 1 (XBP1). Together, our study suggests that PM2.5 exposure differentially activates the UPR branches, leading to ER stress-induced apoptosis through the PERK-eIF2 alpha-CHOP UPR branch. This work provides novel insights into the cellular and molecular basis by which ambient PM2.5 exposure elicits its cytotoxic effects that may be related to air pollution-associated pathogenesis.