title: The effect of ASK1 on vascular permeability and edema formation in cerebral ischemia.
abstract: Apoptosis signal-regulating kinase-1 (ASK1) is the mitogen-activated protein kinase kinase kinase (MAPKKK) and participates in the various central nervous system (CNS) signaling pathways. In cerebral ischemia, vascular permeability in the brain is an important issue because regulation failure of it results in edema formation and blood-brain barrier (BBB) disruption. To determine the role of ASK1 on vascular permeability and edema formation following cerebral ischemia, we first investigated ASK1-related gene expression using microarray analyses of ischemic brain tissue. We then measured protein levels of ASK1 and vascular endothelial growth factor (VEGF) in brain endothelial cells after hypoxia injury. We also examined protein expression of ASK1 and VEGF, edema formation, and morphological alteration through cresyl violet staining in ischemic brain tissue using ASK1-small interference RNA (ASK1-siRNA). Finally, immunohistochemistry was performed to examine VEGF and aquaporin-1 (AQP-1) expression in ischemic brain injury. Based on our findings, we propose that ASK1 is a regulating factor of vascular permeability and edema formation in cerebral ischemia.
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Juhyun
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul, South Korea; BK21 Plus Project for Medical Sciences, and Brain Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: So Yeong
authors.initials: SY
authors.lastname: Cheon
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Won Taek
authors.initials: WT
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Kyung Ah
authors.initials: KA
authors.lastname: Park
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul, South Korea; BK21 Plus Project for Medical Sciences, and Brain Research Institute, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: jelee@yuhs.ac.
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Lee
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology*; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000172:deficiency; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000494:pharmacology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D051398:Aquaporin 1; D005947:Glucose
keywords: Apoptosis signal-regulating kinase 1 (ASK1); Aquaporin-1 (AQP-1); Blood–brain barrier (BBB); Cerebral ischemia; Edema; Vascular endothelial growth factor (VEGF); Vascular permeability