Effects of transient focal cerebral ischemia in mice deficient in puma.
Bcl-2 homology domain 3 (BH3)-only pro-apoptotic proteins may play an important role in upstream cell death signaling pathways underlying ischemic brain injury. Puma is a potent BH3-only protein that can be induced via p53, FoxO3a and endoplasmic reticulum stress pathways and is upregulated by global cerebral ischemia. To more completely define the contribution of Puma to ischemic brain injury we measured the expressional response of Puma to transient focal cerebral ischemia in mice and also compared infarct volumes in puma-deficient versus puma-expressing mice. Real-time quantitative PCR determined puma mRNA levels were significantly increased 8h after 90min middle cerebral artery (MCA) occlusion in the ipsilateral cortex, while expression remained unchanged contralaterally. Puma protein levels were also increased in the ischemic cortex over the same period. However, cortical and striatal infarct volumes were not significantly different between puma-deficient and puma-expressing mice at 24h, and no differences between genotypes were found for post-ischemic neurological deficit scores. These data demonstrate that focal cerebral ischemia is associated with puma induction but suggest that Puma does not contribute significantly to lesion development in the present model.
Kuroki
Katsura
K
Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Virard
Isabelle
I
Concannon
Caoimhin G
CG
Engel
Tobias
T
Woods
Ina
I
Taki
Waro
W
Plesnila
Nikolaus
N
Henshall
David C
DC
Prehn
Jochen H M
JH
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016923:Cell Death / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D002544:Cerebral Infarction / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D003342:Corpus Striatum / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D004185:Disability Evaluation; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; C488588:PUMA protein, mouse; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins