Astrocytic CCAAT/Enhancer-binding protein delta contributes to reactive oxygen species formation in neuroinflammation
Shao-Ming Wang,
Sher-Wei Lim,
Ya-Han Wang,
Hong-Yi Lin,
Ming-Derg Lai,
Chiung-Yuan Ko,
Ju-Ming Wang
Affiliations
Shao-Ming Wang
Institute of Basic Medical Sciences, College of Medicine, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan; Center for Neurotrauma and Neuroregeneration, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
Sher-Wei Lim
Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan; Departments of Neurosurgery, Chi-Mei Medical Center, Tainan 722, Taiwan; Department of Nursing, Min-Hwei College of Health Care Management, Tainan 736, Taiwan
Ya-Han Wang
Department of Life Science, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan
Hong-Yi Lin
The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan
Ming-Derg Lai
Institute of Basic Medical Sciences, College of Medicine, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan
Chiung-Yuan Ko
Center for Neurotrauma and Neuroregeneration, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Corresponding author at: Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
Ju-Ming Wang
Institute of Basic Medical Sciences, College of Medicine, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan; Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan; Graduate Institute of Medical Sciences, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Corresponding author at: Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.
Excessive reactive oxygen species (ROS) can form an oxidative stress and an associated neuroinflammation. However, the contribution of astrocytes to ROS formation, the cause of the resistance of astrocytes to oxidative stress, and the consequences on neurons remain largely uninvestigated. The transcription factor CCAAT/enhancer-binding protein delta (CEBPD) is highly expressed in astrocytes and has been suggested to contribute to the progress of Alzheimer's disease (AD). In this study, we found that ROS formation and expression of p47phox and p67phox, subunits of NADPH oxidase, were increased in AppTg mice but attenuated in AppTg/Cebpd-/- mice. Cebpd can up-regulate p47phox and p67phox transcription via a direct binding on their promoters, which results in an increase in intracellular oxidative stress. In addition, Cebpd also up-regulated Cu/Zn superoxide dismutase (Sod1) in astrocytes. Inactivation of Sod1 increased the sensitization to oxidative stress, which provides a reason for the resistance of astrocytes in an oxidative stress environment. Taken together, the study first revealed and dissected the involvement of astrocytic Cebpd in the promotion of oxidative stress and the contribution of CEBPD to the resistance of astrocytes in an oxidative stress environment. Keywords: ROS, Astrocyte, CEBPD, SOD1 and neuroinflammation
