Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294-0017, USA.
Neurobiol Dis. 2010 Sep;39(3):334-43. doi: 10.1016/j.nbd.2010.04.018. Epub 2010 May 6.
Transglutaminase 2 (TG2) is a multifunctional protein that modulates cell survival and death pathways. It is upregulated in numerous ischemic models, and protects primary neurons from oxygen and glucose deprivation. TG2 binds to the hypoxia inducible factor (HIF) 1beta and decreases the upregulation of hypoxic-induced proapoptotic genes. To investigate the role of TG2 in ischemic stroke in vivo, we used the murine, permanent middle cerebral artery (MCA) ligation model. TG2 mRNA levels are increased after MCA ligations, and transgenic mice that express human TG2 in neurons had significantly smaller infarct volumes than wild type littermates. Further, TG2 translocates into the nucleus within 2h post ligation. Nuclear-localized TG2 is also apparent in human stroke cases. TG2 suppressed the upregulation of the HIF-induced, proapoptotic gene, Noxa. The findings of this study indicate that TG2 plays a role in attenuating ischemic-induced cell death possibly by modulating hypoxic-induced transcriptional processes.
转谷氨酰胺酶 2（TG2）是一种多功能蛋白，可调节细胞存活和死亡途径。它在许多缺血模型中上调，并保护原代神经元免受缺氧和葡萄糖剥夺。TG2 与缺氧诱导因子（HIF）1β结合，降低缺氧诱导的促凋亡基因的上调。为了研究 TG2 在体内缺血性中风中的作用，我们使用了小鼠永久性大脑中动脉（MCA）结扎模型。MCA 结扎后 TG2mRNA 水平升高，表达人 TG2 的神经元转基因小鼠的梗死体积明显小于野生型同窝小鼠。此外，TG2 在结扎后 2 小时内转移到核内。在人类中风病例中也明显存在核定位的 TG2。TG2 抑制了 HIF 诱导的促凋亡基因 Noxa 的上调。这项研究的结果表明，TG2 通过调节缺氧诱导的转录过程，在减轻缺血诱导的细胞死亡中发挥作用。
