BAY 73-6691 Alters Neuron Plasticity and Phosphorylation of Tau Through Regulation of Cyclic Guanosine Monophosphate/Protein Kinase G/Cyclic Adenosine Monophosphate Response Element-Binding Protein Pathway

被引:0
|
作者
Jiang, Hui [1 ]
Zheng, Yan [1 ]
Ni, Jie [2 ]
Xu, Yun [3 ]
机构
[1] Affiliated Hosp Nanjing Univ Chinese Med, Jiangsu Prov Hosp Chinese Med, Dept Neurol, Nanjing 210000, Jiangsu, Peoples R China
[2] Nanjing Univ, Affiliated Drum Tower Hosp, Dept Emergency, Nanjing 210000, Peoples R China
[3] Nanjing Univ, Dept Neurol, Affiliated Drum Tower Clin Med Coll, Nanjing 210000, Peoples R China
关键词
BAY; 73-6691; Alzheimer's Disease; Apoptosis; Inflammation; Synaptic Protein; PAIRED HELICAL FILAMENTS; ALZHEIMERS-DISEASE; SYNAPTIC PLASTICITY; IN-VITRO; PHOSPHODIESTERASE INHIBITORS; CGMP; EXPRESSION; SUBUNIT; PEPTIDE; MODEL;
D O I
10.1166/jbt.2021.2539
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Alzheimer's disease (AD) is one of neurodegenerative diseases characterized by cognitive and memory decline, accompanying with neurofibrillary tangles (NFTs) made of hyperphosphorylated tau protein and senile plaques (SP) accumulated by beta-amyloid protein (A beta). BAY 73-6691, an inhibitor of phosphodiesterase-9 (PDE-9), can improve learning and memory of elderly rats. However, the effects of BAY 73-6691 on neuroapoptotic and neuroinflammatory events, as well as synaptic plasticity of differentiated PC12 cells are remain unclear. In this work, we screened apoptotic cells induced by A beta(25-35) via flow cytometry. TNF-alpha, IL-1 beta, IL-6 secreted by PC12 cells were estimated by ELISA kits. The levels of cGMP, PKG and CREB mediated by BAY 73-6691 were assessed. Moreover, we conducted western blots analysis to evaluate the phosphorylation of tau and synaptic related proteins. Results showed that BAY 73-6691 could reduce A beta(25-35)-triggered neuroapoptosis and neuroinflammation. Phosphorylation of tau was inhibited by BAY 73-6691, whereas sildenafil citrate (SC, an inhibitor of cGMP) partially weakened the effect of BAY 73-6691. Additionally, synaptic plasticity restored by BAY 73-6691 was also suppressed via SC. Taken together, BAY 73-6691 exhibited neuroprotective effects, and altered tau phosphorylation as well as synaptic related proteins through cGMP/PKG/CREB pathway.
引用
收藏
页码:295 / 301
页数:7
相关论文
共 50 条
  • [21] Update and Potential Opportunities in CBP [Cyclic Adenosine Monophosphate (cAMP) Response Element-Binding Protein (CREB)-Binding Protein] Research Using Computational Techniques
    Oluwayimika E. Akinsiku
    Opeyemi S. Soremekun
    Mahmoud E. S. Soliman
    The Protein Journal, 2021, 40 : 19 - 27
  • [22] Isoflurane Inhibits Cyclic Adenosine Monophosphate Response Element-Binding Protein Phosphorylation and Calmodulin Translocation to the Nucleus of SH-SY5Y Cells
    Zhang, Jin
    Sutachan, Jhon-Jairo
    Montoya-Gacharna, Jose
    Xu, Chong-Feng
    Xu, Fang
    Neubert, Thomas A.
    Recio-Pinto, Esperanza
    Blanck, Thomas J. J.
    ANESTHESIA AND ANALGESIA, 2009, 109 (04): : 1127 - 1134
  • [23] Inhibition of the cyclic adenosine monophosphate pathwav attenuates neuropathic pain and reduces phosphorylation of cyclic adenosine monophosphate response element-binding in the spinal cord after partial sciatic nerve Ligation in rats
    Liou, Jiin-Tarng
    Liu, Fu-Chao
    Hsin, Shi-Tai
    Yang, Ching-Yue
    Lui, Ping-Wing
    ANESTHESIA AND ANALGESIA, 2007, 105 (06): : 1830 - 1837
  • [24] A novel cell-based assay for G-protein-coupled receptor-mediated cyclic adenosine monophosphate response element binding protein phosphorylation
    Selkirk, Julie V.
    Nottebaum, Lisa M.
    Ford, Ian C.
    Santos, Mark
    Malany, Siobhan
    Foster, Alan C.
    Lechner, Sandra M.
    JOURNAL OF BIOMOLECULAR SCREENING, 2006, 11 (04) : 351 - 358
  • [25] A Novel Role for Thyroid-Stimulating Hormone: Up-Regulation of Hepatic 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A Reductase Expression Through the Cyclic Adenosine Monophosphate/Protein Kinase A/Cyclic Adenosine Monophosphate Responsive Element Binding Protein Pathway
    Tian, Limin
    Song, Yongfeng
    Xing, Mingzhao
    Zhang, Wei
    Ning, Guang
    Li, Xiaoying
    Yu, Chunxiao
    Qin, Chengkong
    Liu, Jun
    Tian, Xingsong
    Sun, Xinglan
    Fu, Rui
    Zhang, Lin
    Zhang, Xiujuan
    Lu, Yan
    Zou, Jianwen
    Wang, Laicheng
    Guan, Qingbo
    Gao, Ling
    Zhao, Jiajun
    HEPATOLOGY, 2010, 52 (04) : 1401 - 1409
  • [26] The endothelial nitric oxide synthase/cyclic guanosine monophosphate/protein kinase G pathway activates primordial follicles
    Zhao, Peikun
    Song, Zidai
    Wang, Yan
    Cai, Han
    Du, Xiaoyan
    Li, Changlong
    Lv, Jianyi
    Liu, Xin
    Guo, Meng
    Chen, Zhenwen
    AGING-US, 2021, 13 (01): : 1096 - 1119
  • [27] A BINDING-SITE FOR THE CYCLIC ADENOSINE 3',5'-MONOPHOSPHATE-RESPONSE ELEMENT-BINDING PROTEIN AS A REGULATORY ELEMENT IN THE GRP78-PROMOTER
    ALEXANDRE, S
    NAKAKI, T
    VANHAMME, L
    LEE, AS
    MOLECULAR ENDOCRINOLOGY, 1991, 5 (12) : 1862 - 1872
  • [28] Inhibition of Cyclic Adenosine Monophosphate (cAMP)-Response Element-Binding Protein (CREB)-Binding Protein (CBP)/β-Catenin Directly Attenuates the Hepatocytes-Mediated Fibrogenesis
    Mizutani, Yuki
    Kimura, Kiminori
    Kouji, Hiroyuki
    Koga, Hironori
    Hrada, Kenichi
    LABORATORY INVESTIGATION, 2017, 97 : 420A - 420A
  • [29] Phosphorylation of cyclic adenosine monophosphate response element binding protein in oligodendrocytes in the corpus callosum after focal cerebral ischemia in the rat
    Tanaka, K
    Nogawa, S
    Ito, D
    Suzuki, S
    Dembo, T
    Kosakai, A
    Fukuuchi, Y
    JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2001, 21 (10): : 1177 - 1188
  • [30] Inhibition of Cyclic Adenosine Monophosphate (cAMP)-Response Element-Binding Protein (CREB)-Binding Protein (CBP)/β-Catenin Directly Attenuates the Hepatocytes-Mediated Fibrogenesis
    Mizutani, Yuki
    Kimura, Kiminori
    Kouji, Hiroyuki
    Koga, Hironori
    Hrada, Kenichi
    MODERN PATHOLOGY, 2017, 30 : 420A - 420A