Neuroglobin-overexpressing transgenic mice are resistant to cerebral and myocardial ischemia.
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.
Khan
Adil A
AA
Buck Institute for Age Research, Novato, CA 94945, USA.
Wang
Yaoming
Y
Sun
Yunjuan
Y
Mao
Xiao Ou
XO
Xie
Lin
L
Miles
Erin
E
Graboski
Justin
J
Chen
Sylvia
S
Ellerby
Lisa M
LM
Jin
Kunlin
K
Greenberg
David A
DA
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
D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D005914:Globins