c-Myc signaling networks of diffuse alveolar damage (DAD) induced by oxygen poisoning

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460875
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Legal medicine
• Research Institution: University of Fukui
• Principal Investigator: Shimada Ichiroh 福井大学, 学術研究院医学系部門, 教授 (20272908)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 高濃度酸素曝露 / 瀰漫性肺胞傷害 / c-Myc / Bax / 肺サーファクタント蛋白 / カスパーゼ / 活性酸素種 / アポトーシス

Outline of Final Research Achievements

Hyperoxia induced a decrease in SP-C/A expression in mouse lungs, and the SP-C downregulation was also confirmed in A549 cells. In addition to enhanced c-Myc expression, Bax expression also increased following mouse exposure to hyperoxia. In vitro analysis showed that expression of these genes was regulated in a cell-type-dependent manner, i.e., upregulation of c-Myc in NIH/3T3 cells and Bax in A549 cells occurred regardless of whether there was a similar decrease in cell viability and increase in caspase-3/7 activation in response to hyperoxia. ROS production and caspase-8 activation were also detected in both cells.
We concluded that hyperoxia induces ROS production and cell death in lung tissues through a cell-type specific mechanism involving upregulation of c-Myc/Bax, and caspase-8 and -3/7 activation-dependent pathways, thereby leading to the development of diffuse alveolar damage (DAD).

Free Research Field

法医病理学