Elevation of neuronal expression of NAIP reduces ischemic damage in the rat hippocampus.
We show here that transient forebrain ischemia selectively elevates levels of neuronal apoptosis inhibitory protein (NAIP) in rat neurons that are resistant to the injurious effects of this treatment. This observation suggests that increasing NAIP levels may confer protection against ischemic cell death. Consistent with this proposal, we demonstrate that two other treatments that increase neuronal NAIP levels, systemic administration of the bacterial alkaloid K252a and intracerebral injection of an adenovirus vector capable of overexpressing NAIP in vivo, reduce ischemic damage in the rat hippocampus. Taken together, these findings suggest that NAIP may play a key role in conferring resistance to ischemic damage and that treatments that elevate neuronal levels of this antiapoptotic protein may have utility in the treatment of stroke.
Xu
D G
DG
Department of Cellular and Molecular Medicine, University of Ottawa, Ontario, Canada.
Crocker
S J
SJ
Doucet
J P
JP
St-Jean
M
M
Tamai
K
K
Hakim
A M
AM
Ikeda
J E
JE
Liston
P
P
Thompson
C S
CS
Korneluk
R G
RG
MacKenzie
A
A
Robertson
G S
GS
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002227:Carbazoles / Q000008:administration & dosage / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects; D015316:Genetic Therapy; D005822:Genetic Vectors; D006624:Hippocampus / Q000098:blood supply / Q000293:injuries* / Q000378:metabolism*; D026121:Indole Alkaloids; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008297:Male; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000627:therapeutic use; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D051616:Neuronal Apoptosis-Inhibitory Protein; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D002227:Carbazoles; D026121:Indole Alkaloids; C496803:Naip6 protein, rat; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; C049985:staurosporine aglycone