Association of 14-3-3gamma and phosphorylated bad attenuates injury in ischemic astrocytes.
Our recent findings indicate an induced upregulation of 14-3-3gamma mRNA and protein in ischemic cortical astrocytes. Despite being brain-specific, the functional role of 14-3-3gamma in the brain still remains largely unknown. In this study, we show that among all the 14-3-3 isoforms, only the gamma isoform is inducible under ischemia in astrocytes. Furthermore, this upregulation of 14-3-3gamma may play a specific protective role in astrocytes under ischemia. Overexpression experiments and antisense treatment show that an elevation of 14-3-3gamma protein in astrocytes promotes survival, while a decrease in 14-3-3gamma enhances apoptosis in astrocytes under ischemia. Under ischemia, endogenous 14-3-3gamma binds p-Bad, thus preventing Bad from entering mitochondria to initiate apoptosis. Therefore, 14-3-3gamma is selectively induced during ischemia to protect astrocytes from apoptosis through p-Bad-related signaling.
Chen
Xiao Qian
XQ
Neuroscience Research Institute, Peking University, Beijing, China.
Fung
Yin-Wan Wendy
YW
Yu
Albert Cheung Hoi
AC
D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D002352:Carrier Proteins / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051025:bcl-Associated Death Protein
D048948:14-3-3 Proteins; C494820:Bad protein, mouse; D002352:Carrier Proteins; D012333:RNA, Messenger; D051025:bcl-Associated Death Protein