PMID- 24072482 OWN - NLM STAT- MEDLINE DCOM- 20141006 LR - 20211021 IS - 1559-1166 (Electronic) IS - 0895-8696 (Linking) VI - 52 IP - 2 DP - 2014 Feb TI - Activating transcription factor 4 modulates BDNF release from microglial cells. PG - 225-30 LID - 10.1007/s12031-013-0126-1 [doi] AB - Pathogenic pain is a common sign of many diseases. The mechanism is unclear. Activating transcription factor 4 (ATF4) plays a critical role in cell activation. Brain-derived neurotrophic factor (BDNF) is an important molecule in pathogenic pain. This study aims to investigate the role of ATF4 in inducing BDNF release from microglial cells. In this study, mouse microglial cells were cultured. The levels of BDNF in the culture medium were determined by enzyme-linked immunosorbent assay. Overexpression of ATF4 in microglial cells was performed by gene transfection. The apoptosis of microglial cells was assessed by flow cytometry. The results showed that microglial cells expressed ATF4 and protease-activated receptor-2 (PAR2). BDNF was detectable in the culture medium of microglial cells, which was significantly increased in the ATF4-overexpressing microglial cells. The ATF4-overexpressing microglial cells showed a high frequency of apoptotic cells, which could be inhibited by exposure to the PAR2 agonist tryptase in the culture. The tryptase-treated ATF4-overexpressing microglial cells kept higher secretion of BDNF. We conclude that the activation of ATF4 can increase BDNF release from microglial cells. FAU - Sun, Pengling AU - Sun P AD - Department of Anesthesiology, Neuroscience Research Centre, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China. FAU - Li, Xiangnan AU - Li X FAU - Chen, Chengwen AU - Chen C FAU - Chen, Qianbo AU - Chen Q FAU - Ouyang, Qing AU - Ouyang Q FAU - Liu, Fangting AU - Liu F FAU - Xiang, Zhenghua AU - Xiang Z FAU - Yuan, Hongbin AU - Yuan H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130927 PL - United States TA - J Mol Neurosci JT - Journal of molecular neuroscience : MN JID - 9002991 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptor, PAR-2) RN - 145891-90-3 (Activating Transcription Factor 4) SB - IM MH - Activating Transcription Factor 4/genetics/*metabolism MH - Animals MH - Apoptosis MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Cell Line MH - Mice MH - Microglia/*metabolism/physiology MH - Receptor, PAR-2/genetics/metabolism EDAT- 2013/09/28 06:00 MHDA- 2014/10/07 06:00 CRDT- 2013/09/28 06:00 PHST- 2013/08/03 00:00 [received] PHST- 2013/09/16 00:00 [accepted] PHST- 2013/09/28 06:00 [entrez] PHST- 2013/09/28 06:00 [pubmed] PHST- 2014/10/07 06:00 [medline] AID - 10.1007/s12031-013-0126-1 [doi] PST - ppublish SO - J Mol Neurosci. 2014 Feb;52(2):225-30. doi: 10.1007/s12031-013-0126-1. Epub 2013 Sep 27.