title: AMPK Plays a Dual Role in Regulation of CREB/BDNF Pathway in Mouse Primary Hippocampal Cells.
abstract: The hippocampus is vulnerable to damage under conditions of ischemia and hypoxia, causing multiple mental illnesses. cAMP response element-binding protein (CREB) plays a pivotal role in preventing the apoptosis of neurons and many other cells. Here, we found that AMP-activated protein kinase (AMPK) and CREB are oppositely regulated in mouse primary hippocampal neurons impaired by hypoxia-hypoglycemia. AMPK overexpression reduced the CREB level by upregulating SIRT1 and was negatively posttranscriptionally regulated by miR-134, suggesting a negative regulatory role of AMPK in the expression of CREB. Interestingly, the downstream genes of CREB, brain-derived neurotrophic factor (BDNF), and Bcl-2 remained unchanged when CREB was downregulated by AMPK expression. In addition, in AMPK(-/-) primary hippocampal neurons, comparisons between the effect of upregulation and silencing of miR-134 on the expression of CREB, BDNF, and Bcl-2 were made. The results reveal that AMPK is crucial for the activation of CREB via phosphorylation. Therefore, AMPK plays a dual role in the regulation of CREB in mouse primary hippocampal cells: a negative effect on total CREB expression by elevating SIRT1/miR-134 and a positive effect on activity via phosphorylation.
authors: Department of Neurosurgery, Shaanxi Provincial People's Hospital, 256 Youyi West Road, Huangyancun, Beilin District, Xian, 710068, China. weidonghuangsx@163.com.
authors: Weidong
authors: W
authors: Huang
authors: Department of Neurosurgery, Shaanxi Provincial People's Hospital, 256 Youyi West Road, Huangyancun, Beilin District, Xian, 710068, China.
authors: Jie
authors: J
authors: Cao
authors: Department of Neurosurgery, Shaanxi Provincial People's Hospital, 256 Youyi West Road, Huangyancun, Beilin District, Xian, 710068, China.
authors: Xiaobin
authors: X
authors: Liu
authors: Department of Neurosurgery, Shaanxi Provincial People's Hospital, 256 Youyi West Road, Huangyancun, Beilin District, Xian, 710068, China.
authors: Facai
authors: F
authors: Meng
authors: Department of Neurosurgery, Shaanxi Provincial People's Hospital, 256 Youyi West Road, Huangyancun, Beilin District, Xian, 710068, China.
authors: Min
authors: M
authors: Li
authors: Department of Neurosurgery, Shaanxi Provincial People's Hospital, 256 Youyi West Road, Huangyancun, Beilin District, Xian, 710068, China.
authors: Bo
authors: B
authors: Chen
authors: Department of Neurosurgery, Shaanxi Provincial People's Hospital, 256 Youyi West Road, Huangyancun, Beilin District, Xian, 710068, China.
authors: Jie
authors: J
authors: Zhang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D035683:MicroRNAs; C551912:Mirn134 microRNA, mouse; D055372:AMP-Activated Protein Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
references: FEBS Lett. 2000 Sep 29;482(1-2):44-8
references: 11018520
references: J Biol Chem. 2002 Jul 12;277(28):25226-32
references: 11994296
references: Nat Rev Mol Cell Biol. 2007 Oct;8(10):774-85
references: 17712357
references: J Neurosci Res. 2000 Jan 1;59(1):107-16
references: 10658191
references: Brain Res. 2009 Feb 27;1257:75-88
references: 19100722
references: Mol Pharmacol. 2009 Oct;76(4):896-902
references: 19620255
references: Cell Signal. 2005 Nov;17 (11):1343-51
references: 16125054
references: Cancer Res. 2008 Feb 15;68(4):981-8
references: 18281471
references: Steroids. 2009 Jul;74(7):555-61
references: 19428444
references: BMC Neurosci. 2009 Sep 28;10:123
references: 19785755
references: J Clin Invest. 2001 Oct;108(8):1167-74
references: 11602624
references: Ageing Res Rev. 2012 Apr;11(2):230-41
references: 22186033
references: Toxicology. 2014 Sep 2;323:95-108
references: 24973631
references: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13217-21
references: 12244210
references: Nature. 2011 Feb 17;470(7334):404-8
references: 21331044
references: J Mol Neurosci. 2015 Apr;55(4):821-9
references: 25316150
references: Food Chem Toxicol. 2014 Sep;71:81-9
references: 24937021
references: Nature. 2009 Apr 23;458(7241):1056-60
references: 19262508
references: Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12553-8
references: 20616029
references: Int J Cancer. 2006 Mar 15;118(6):1370-80
references: 16206275
references: Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):15983-7
references: 12444247
references: Neuroscience. 2014 Sep 5;275:455-68
references: 24972302
references: J Neurosci. 2012 Aug 15;32(33):11390-5
references: 22895721
references: Nature. 2010 Aug 26;466(7310):1105-9
references: 20622856
references: Acta Pharmacol Sin. 2010 Mar;31(3):265-72
references: 20154710