Attenuation of ischemia-induced mouse brain injury by SAG, a redox-inducible antioxidant protein

Guo Yuan Yang, Li Pang, Hai Liang Ge, Mingjia Tan, Wen Ye, Xiao Hong Liu, Feng Ping Huang, Du Chu Wu, Xiao Ming Che, Ying Song, Rong Wen, Yi Sun

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Cerebral ischemia resulting from a disruption of blood flow to the brain initiates a cascade of events that causes neuron death and leads to neurologic dysfunction. Reactive oxygen species are thought, at least in part, to mediate this disease process. The authors recently cloned and characterized an antioxidant protein, SAG (sensitive to apoptosis gene), that is redox inducible and protects cells from apoptosis induced by redox agents in a number of in vitro cell model systems. This study reports a neuroprotective role of SAG in ischemia/reperfusion-induced brain injury in an in vivo mouse model. SAG was expressed at a low level in brain tissue and was inducible after middle cerebral artery occlusion with peak expression at 6 to 12 hours. At the cellular level, SAG was mainly expressed in the cytoplasm of neurons and astrocytes, revealed by double immunofluorescence. An injection of recombinant adenoviral vector carrying human SAG into mouse brain produced an overexpression of SAG protein in the injected areas. Transduction of AdCMVSAG (wild-type), but not AdCMVmSAG (mutant), nor the AdCMVlacZ control, protected brain cells from ischemic brain injury, as evidenced by significant reduction of the infarct areas where SAG was highly expressed. The result suggests a rather specific protective role of SAG in the current in vivo model. Mechanistically, SAG overexpression decreased reactive oxygen species production and reduced the number of apoptotic cells in the ischemic areas. Thus, antioxidant SAG appears to protect against reactive oxygen species-induced brain damage in mice. Identification of SAG as a neuroprotective molecule could lead to potential stroke therapies.

Original languageEnglish (US)
Pages (from-to)722-733
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume21
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Adenovirus
  • Apoptosis
  • Gene transfer
  • Middle cerebral artery occlusion
  • Reactive oxygen species

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

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