Reduction of ischemic damage in NGF-transgenic mice: correlation with enhancement of antioxidant enzyme activities.
If permanent focal ischemia is induced by middle cerebral artery occlusion (MCAO), neurons within the infarcted territory die by necrosis and apoptosis (or programmed cell death). We have previously shown, using a mouse strain transgenic (tg) for the nerve growth factor (NGF) gene, that tg mice have consistently smaller infarcted areas than wild-type (wt) animals, correlated with upregulated NGF synthesis and impaired apoptotic cell death. We studied, in wt and tg mice subjected to MCAO, the activities of several antioxidant enzymes and the synthesis of the proteins of the Bcl-2 family. Our results show that the antiapoptotic Bcl-2 protein and glutathione peroxidase are recruited after MCAO. NGF-tg mice also had an intrinsic resistance to oxidative stress because their basal copper zinc superoxide dismutase (SOD) and glutathione transferase activities were high. Additionally, manganese SOD activity increased in NGF-tg mice after MCAO, correlating strongly with the resistance of these mice to apoptosis.
Guégan
C
C
Laboratoire de Neurosciences, Université de Caen, CNRS UMR 6551, France.
Ceballos-Picot
I
I
Chevalier
E
E
Nicole
A
A
Onténiente
B
B
Sola
B
B
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D002352:Carrier Proteins / Q000032:analysis; D002540:Cerebral Cortex / Q000098:blood supply / Q000737:chemistry / Q000201:enzymology; D002544:Cerebral Infarction / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013482:Superoxide Dismutase / Q000378:metabolism*; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein
D000975:Antioxidants; C494820:Bad protein, mouse; C494773:Bak1 protein, mouse; C494812:Bcl2l1 protein, mouse; D002352:Carrier Proteins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase