机构：[a]Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, USA,[b]Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing,神经外科首都医科大学宣武医院[c]China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China中美神经科学研究所首都医科大学宣武医院
Background/Aims: The endogenous neurotrophic peptides pituitary adenylate cyclase-activating polypeptides (PACAP-27/38) protect against stroke, but the molecular mechanism remains unknown. Methods: Primary rat neural cells were exposed to PACAP-27 or PACAP-38 before induction of experimental acute ischemic stroke via oxygen-glucose deprivation-reperfusion (OGD/R) injury. To reveal PACAP's role in neuroprotection, we employed fluorescent live/dead cell viability and caspase 3 assays, optical densitometry of mitochondrial dehydrogenase and cell growth, glutathione disulfide luciferase activity, ELISA for high mobility group box1 extracellular concentration, ATP bioluminescence, Western blot analysis of PACAP, NMDA subunits, apoptosis regulator Bcl-2, social interaction hormone oxytocin, and trophic factor BDNF, and immunocytochemical analysis of PACAP. Results: Both PACAP-27 and PACAP-38 (PACAP-27/38) increased cell viability, decreased oxidative stress-induced cell damage, maintained mitochondrial activity, prevented the release of high mobility group box1, and reduced cytochrome c/caspase 3-induced apoptosis. PACAP-27/38 increased the protein expression levels of BDNF, Bcl-2, oxytocin, and precursor PACAP. N-methyl-D-aspartate receptor (NMDAR)-induced excitotoxicity contributes to the cell death associated with stroke. PACAP-27/38 modulated the protein expression levels of NMDAR subunits. PACAP-27/38 increased the protein expression levels of the GluN1 subunit, and decreased that of the GluN2B and GluN2D subunits. PACAP-27, but not PACAP-38, increased the expression level of the GluN2C subunit. Conclusion: This study provides evidence that PACAP regulated NMDAR subunits, affording neuroprotection after OGD/R injury. (C) 2018 The Author(s) Published by S. Karger AG, Basel
基金：
This study was funded by National Institutes of Health 1R21NS089851 and National
Institutes of Health 5R01NS071956.
第一作者机构：[a]Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, USA,
通讯作者：
通讯机构：[*1]Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, University of South Florida College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612 (USA)
推荐引用方式(GB/T 7714)：
Yuji Kaneko,Julian P. Tuazon,Xunming Ji,et al.Pituitary Adenylate Cyclase Activating Polypeptide Elicits Neuroprotection Against Acute Ischemic Neuronal Cell Death Associated with NMDA Receptors[J].CELLULAR PHYSIOLOGY AND BIOCHEMISTRY.2018,51(4):1982-1995.doi:10.1159/000495722.
APA：
Yuji Kaneko,Julian P. Tuazon,Xunming Ji&Cesario V. Borlongan.(2018).Pituitary Adenylate Cyclase Activating Polypeptide Elicits Neuroprotection Against Acute Ischemic Neuronal Cell Death Associated with NMDA Receptors.CELLULAR PHYSIOLOGY AND BIOCHEMISTRY,51,(4)
MLA：
Yuji Kaneko,et al."Pituitary Adenylate Cyclase Activating Polypeptide Elicits Neuroprotection Against Acute Ischemic Neuronal Cell Death Associated with NMDA Receptors".CELLULAR PHYSIOLOGY AND BIOCHEMISTRY 51..4(2018):1982-1995
