Neuroglobin-overexpressing transgenic mice are resistant to cerebral and myocardial ischemia

Adil A. Khan, Yaoming Wang, Yunjuan Sun, Ou Mao Xiao, Lin Xie, Erin Miles, Justin Graboski, Sylvia Chen, Lisa M. Ellerby, Kunlin Jin, David A. Greenberg

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176 Scopus citations

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 β-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 lit-termates, the volume of cerebral infarcts after occlusion of the middle cerebral artery was reduced by ≈30%, and the volume of myocardial infarcts produced by occlusion of the left anterior descending coronary artery was reduced by ≈=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.

Original languageEnglish
Pages (from-to)17944-17948
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number47
DOIs
StatePublished - 21 Nov 2006

Keywords

  • Endothelial nitric oxide synthase
  • Myocardial infarction
  • Stroke

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    Khan, A. A., Wang, Y., Sun, Y., Xiao, O. M., Xie, L., Miles, E., Graboski, J., Chen, S., Ellerby, L. M., Jin, K., & Greenberg, D. A. (2006). Neuroglobin-overexpressing transgenic mice are resistant to cerebral and myocardial ischemia. Proceedings of the National Academy of Sciences of the United States of America, 103(47), 17944-17948. https://doi.org/10.1073/pnas.0607497103