Viral caspase inhibitor p35, but not crmA, is neuroprotective in the ischemic penumbra following experimental stroke.
Apoptosis, a predominant cause of neuronal death after stroke, can be executed in a caspase-dependent or apoptosis inducing factor (AIF)-dependent manner. Herpes simplex virus (HSV) vectors expressing caspase inhibitors p35 and crmA have been shown to be neuroprotective against various excitotoxic insults. Here we further evaluated the possible neuroprotective role of p35 and crmA in a rat stroke model. Overexpression of p35, but not crmA, significantly increased neuronal survival. Results of double immunofluorescence staining indicate that compared with neurons infected with crmA or control vectors, p35-infected neurons had less active caspase-3 expression, cytosolic cytochrome c and nuclear AIF translocation.
Sung
J H
JH
Department of Neurosurgery, Stanford University, School of Medicine, 300 Pasteur Drive R200, Stanford, CA 94305-5327, USA.
Zhao
H
H
Roy
M
M
Sapolsky
R M
RM
Steinberg
G K
GK
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D007211:Indoles; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology*; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D018139:Simplexvirus / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D001616:beta-Galactosidase
C494831:Aifm1 protein, rat; D051033:Apoptosis Inducing Factor; D007211:Indoles; D015843:Serpins; D014764:Viral Proteins; C492234:p35 protein, Baculovirus; C007293:DAPI; D045304:Cytochromes c; C074641:interleukin-1beta-converting enzyme inhibitor; D001616:beta-Galactosidase; D001973:Bromodeoxyuridine