title: PKA Inhibitor H89 (N-[2-p-bromocinnamylamino-ethyl]-5-isoquinolinesulfonamide) Attenuates Synaptic Dysfunction and Neuronal Cell Death following Ischemic Injury.
abstract: The cyclic AMP-dependent protein kinase (PKA), which activates prosurvival signaling proteins, has been implicated in the expression of long-term potentiation and hippocampal long-term memory. It has come to light that H89 commonly known as the PKA inhibitor have diverse roles in the nervous system that are unrelated to its role as a PKA inhibitor. We have investigated the role of H89 in ischemic and reperfusion injury. First, we examined the expression of postsynaptic density protein 95 (PSD95), microtubule-associated protein 2 (MAP2), and synaptophysin in mouse brain after middle cerebral artery occlusion injury. Next, we examined the role of H89 pretreatment on the expression of brain-derived neurotrophic factor (BDNF), PSD95, MAP2, and the apoptosis regulators Bcl2 and cleaved caspase-3 in cultured neuroblastoma cells exposed to hypoxia and reperfusion injury. In addition, we investigated the alteration of AKT activation in H89 pretreated neuroblastoma cells under hypoxia and reperfusion injury. The data suggest that H89 may contribute to brain recovery after ischemic stroke by regulating neuronal death and proteins related to synaptic plasticity.
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Juhyun
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea ; BK21 Plus Project for Medical Sciences and Brain Research Institute, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: So Yeong
authors.initials: SY
authors.lastname: Cheon
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Won Taek
authors.initials: WT
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Kyung Ah
authors.initials: KA
authors.lastname: Park
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea ; BK21 Plus Project for Medical Sciences and Brain Research Institute, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Lee
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D016923:Cell Death / Q000187:drug effects*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases / Q000235:genetics; D002534:Hypoxia, Brain / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D007546:Isoquinolines / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology; D013449:Sulfonamides / Q000627:therapeutic use*; D013569:Synapses / Q000187:drug effects* / Q000648:ultrastructure
chemical_list: D051017:Apoptosis Regulatory Proteins; D019208:Brain-Derived Neurotrophic Factor; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D007546:Isoquinolines; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D017868:Cyclic AMP-Dependent Protein Kinases; D051528:Guanylate Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide