Kuroki Katsura, Virard Isabelle, Concannon Caoimhin G, Engel Tobias, Woods Ina, Taki Waro, Plesnila Nikolaus, Henshall David C, Prehn Jochen H M
Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Neurosci Lett. 2009 Feb 27;451(3):237-40. doi: 10.1016/j.neulet.2009.01.019. Epub 2009 Jan 13.
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.
仅含Bcl-2同源结构域3（BH3）的促凋亡蛋白可能在缺血性脑损伤潜在的上游细胞死亡信号通路中发挥重要作用。Puma是一种强效的仅含BH3蛋白，可通过p53、FoxO3a和内质网应激途径诱导产生，且在全脑缺血时上调。为了更全面地确定Puma对缺血性脑损伤的作用，我们检测了Puma对小鼠短暂性局灶性脑缺血的表达反应，并比较了Puma缺陷型小鼠和Puma表达型小鼠的梗死体积。实时定量PCR检测显示，大脑中动脉（MCA）闭塞90分钟后8小时，同侧皮质中Puma mRNA水平显著升高，而对侧则无变化。同期缺血皮质中的Puma蛋白水平也升高。然而，在24小时时，Puma缺陷型小鼠和Puma表达型小鼠的皮质和纹状体梗死体积无显著差异，且在缺血后神经功能缺损评分方面未发现基因型差异。这些数据表明，局灶性脑缺血与Puma的诱导有关，但提示在本模型中Puma对损伤发展的作用不显著。
