Increase of Zinc Finger Protein 179 in Response to CCAAT/Enhancer Binding Protein Delta Conferring an Antiapoptotic Effect in Astrocytes of Alzheimer’s Disease

• Published in: Molecular neurobiology 2015-02, Vol.51 (1), p.370-382
• Main Authors: Wang, Shao-Ming, Lee, Yi-Chao, Ko, Chiung-Yuan, Lai, Ming-Derg, Lin, Ding-Yen, Pao, Ping-Chieh, Chi, Jhih-Ying, Hsiao, Yu-Wei, Liu, Tsung-Lin, Wang, Ju-Ming
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Alzheimer Disease - complications; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Animals; Apoptosis - drug effects; Apoptosis - genetics; Astrocytes - drug effects; Astrocytes - metabolism; Astrocytes - pathology; Base Sequence; Binding sites; Biomedical and Life Sciences; Biomedicine; CCAAT-Enhancer-Binding Protein-delta - deficiency; CCAAT-Enhancer-Binding Protein-delta - metabolism; Cell Biology; Cell Line, Tumor; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Down-Regulation - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Humans; Insulin-Like Growth Factor Binding Protein 3 - genetics; Insulin-Like Growth Factor Binding Protein 3 - metabolism; Interleukin-1beta - pharmacology; Kruppel-Like Transcription Factors - metabolism; Male; Methyl Methanesulfonate - pharmacology; Mice, Inbred C57BL; Mitochondrial Proteins - metabolism; Molecular Sequence Data; Neurobiology; Neurology; Neurosciences; Plaque, Amyloid - complications; Plaque, Amyloid - metabolism; Plaque, Amyloid - pathology; Promyelocytic Leukemia Zinc Finger Protein; Proteins; Transcription, Genetic - drug effects
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-014-8714-9

Reactive astrogliosis is a cellular manifestation of neuroinflammation and occurs in response to all forms and severities of the central nervous system (CNS)’s injury and disease. Both astroglial proliferation and antiapoptotic processes are aspects of astrogliosis. However, the underlying mechanism of this response remains poorly understood. In addition, little is known about why activated astrocytes are more resistant to stress and inflammation. CCAAT/enhancer binding protein delta (CEBPD) is a transcription factor found in activated astrocytes that surround β-amyloid plaques. In this study, we found that astrocytes activation was attenuated in the cortex and hippocampus of APPswe/PS1 E9 ( App Tg)/ Cebpd −/− mice. Furthermore, an increase in apoptotic astrocytes was observed in App Tg/ Cebpd −/− mice, suggesting that CEBPD plays a functional role in enhancing the antiapoptotic ability of astrocytes. We found that Zinc Finger Protein 179 (ZNF179) was a CEBPD-regulated gene that played an antiapoptotic, but not proliferative, role in astrocytes. The transcriptions of the proapoptotic genes, insulin-like growth factor binding protein 3 (IGFBP3) and BCL2-interacting killer (BIK), were suppressed by ZNF179 via its interaction with the promyelocytic leukemia zinc finger (PLZF) protein in astrocytes. This study provides the first evidence that ZNF179, PLZF, IGFBP3, and BIK contributed to the novel CEBPD-induced antiapoptotic feature of astrocytes.