title: Neuroglobin-overexpressing transgenic mice are resistant to cerebral and myocardial ischemia.
abstract: Neuroglobin (Ngb), a protein related to myoglobin and hemoglobin but expressed predominantly in the brain, is induced by neuronal hypoxia and cerebral ischemia and protects against hypoxic or ischemic neuronal injury. We engineered transgenic mice that overexpress murine Ngb under the control of a chicken beta-actin promoter, resulting in enhanced Ngb expression in multiple cell types and multiple tissues, including brain and heart. In Ngb-overexpressing transgenic mice compared with wild-type littermates, the volume of cerebral infarcts after occlusion of the middle cerebral artery was reduced by approximately 30%, and the volume of myocardial infarcts produced by occlusion of the left anterior descending coronary artery was reduced by approximately 25%. Ngb overexpression was associated with enhanced expression of endothelial nitric oxide synthase in vascular endothelial cells. These findings extend prior evidence for cytoprotection by Ngb and suggest both direct (parenchymatous) and indirect (vasomotor) protective mechanisms.
authors.affiliation: Buck Institute for Age Research, Novato, CA 94945, USA.
authors.forename: Adil A
authors.initials: AA
authors.lastname: Khan
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Wang
authors.forename: Yunjuan
authors.initials: Y
authors.lastname: Sun
authors.forename: Xiao Ou
authors.initials: XO
authors.lastname: Mao
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.forename: Erin
authors.initials: E
authors.lastname: Miles
authors.forename: Justin
authors.initials: J
authors.lastname: Graboski
authors.forename: Sylvia
authors.initials: S
authors.lastname: Chen
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Ellerby
authors.forename: Kunlin
authors.initials: K
authors.lastname: Jin
authors.forename: David A
authors.initials: DA
authors.lastname: Greenberg
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002645:Chickens; D005914:Globins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000078787:Neuroglobin; D011401:Promoter Regions, Genetic
chemical_list: D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D005914:Globins