Increase of zinc finger protein 179 in response to CCAAT/enhancer binding protein delta conferring an antiapoptotic effect in astrocytes of Alzheimer's disease.
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 (AppTg)/Cebpd (-/-)mice. Furthermore, an increase in apoptotic astrocytes was observed in AppTg/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.
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan.
Shao-Ming
SM
Wang
Yi-Chao
YC
Lee
Chiung-Yuan
CY
Ko
Ming-Derg
MD
Lai
Ding-Yen
DY
Lin
Ping-Chieh
PC
Pao
Jhih-Ying
JY
Chi
Yu-Wei
YW
Hsiao
Tsung-Lin
TL
Liu
Ju-Ming
JM
Wang
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D001483:Base Sequence; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000172:deficiency / Q000378:metabolism*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008297:Male; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D058225:Plaque, Amyloid / Q000150:complications / Q000378:metabolism / Q000473:pathology; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D014158:Transcription, Genetic / Q000187:drug effects
D048868:Adaptor Proteins, Signal Transducing; D016229:Amyloid beta-Peptides; D051017:Apoptosis Regulatory Proteins; C111741:Bik protein, mouse; D004268:DNA-Binding Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D053583:Interleukin-1beta; D051741:Kruppel-Like Transcription Factors; D024101:Mitochondrial Proteins; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C113383:ZNF179 protein, mouse; C513267:Zbtb16 protein, mouse; D051743:CCAAT-Enhancer-Binding Protein-delta; D008741:Methyl Methanesulfonate