Highlighted Paper selected by Editor-in-Chief : Elaidic Acid Potentiates Extracellular ATP-Induced Apoptosis via the P2X₇-ROS-ASK1-p38 Axis in Microglial Cell Lines

DOI Web Site Web Site PubMed 被引用文献7件 参考文献35件
  • Hirata Yusuke
    Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University
  • Nada Yuki
    Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University
  • Yamada Yuto
    Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University
  • Toyama Takashi
    Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University
  • Fukunaga Kohji
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University
  • Hwang Gi-Wook
    Laboratory of Environmental and Health Sciences, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University
  • Noguchi Takuya
    Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University
  • Matsuzawa Atsushi
    Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University

書誌事項

タイトル別名
  • Elaidic Acid Potentiates Extracellular ATP-Induced Apoptosis <i>via</i> the P2X<sub>7</sub>-ROS-ASK1-p38 Axis in Microglial Cell Lines
  • Elaidic Acid Potentiates Extracellular ATP-Induced Apoptosis via the P2X
  • Elaidic acid potentiates extracellular ATP-induced apoptosis via the P2X 7-ROS-ASK1-p38 axis in microglial cell lines

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説明

<p>trans-Fatty acids (TFAs) are unsaturated fatty acids with at least one carbon–carbon double bond in trans configuration. TFA consumption has been epidemiologically associated with neurodegenerative diseases (NDs) including Alzheimer’s disease. However, the underlying mechanisms of TFA-related NDs remain unknown. Here, we show a novel microglial signaling pathway that induces inflammation and cell death, which is dramatically enhanced by elaidic acid (EA), the most abundant TFA derived from food. We found that extracellular ATP, one of the damage-associated molecular patterns (DAMPs) leaked from injured cells, induced activation of the apoptosis signal-regulating kinase 1 (ASK1)-p38 pathway, which is one of the major stress-responsive mitogen-activated protein (MAP) kinase signaling pathways, and subsequent caspase-3 cleavage and DNA ladder formation (hallmarks of apoptosis) in mouse microglial cell lines including BV2 and MG6 cells. Furthermore, we found that in these microglial cell lines, EA, but not its cis isomer oleic acid, facilitated extracellular ATP-induced ASK1/p38 activation and apoptosis, which was suppressed by pharmacological inhibition of either p38, reactive oxygen species (ROS) generation, P2X purinoceptor 7 (P2X7), or Ca2+/calmodulin-dependent kinase II (CaMKII). These results demonstrate that in microglial cells, extracellular ATP induces activation of the ASK1-p38 MAP kinase pathway and ultimately apoptosis downstream of P2X7 receptor and ROS generation, and that EA promotes ATP-induced apoptosis through CaMKII-dependent hyperactivation of the ASK1-p38 pathway, in the same manner as in macrophages. Our study may provide an insight into the pathogenesis of NDs associated with TFAs.</p>

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