Cai Decheng, McCarron Richard M, Yu Erik Z, Li Yingyue, Hallenbeck John
Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 36/ Room 4A03, 36 Convent Drive MSC 4128, Bethesda, MD 20892-4128, USA.
Brain Res. 2004 Jul 16;1014(1-2):14-21. doi: 10.1016/j.brainres.2004.04.008.
Hibernation in mammals is a reversible state of suspended animation associated with tolerance to an otherwise lethal reduction of core body temperature and metabolism. An integral aspect of hibernation is tolerance to a profound decrease of cerebral perfusion. Identification of regulatory mechanisms that control hibernation in ground squirrels can guide efforts to develop improved treatment for stroke and brain trauma. In this study, we show in multiple tissues that S473 phosphorylation of Akt (Protein kinase B), a phosphatidylinositol-3 kinase-regulated serine/threonine kinase, was significantly reduced (P<0.001) as was its kinase activity (P=0.023) in the 13-lined ground squirrel, Spermophilus tridecemlineatus, during hibernation. T308 phosphorylation of Akt was relatively preserved. Brain immunohistochemical staining confirmed these results. In hibernating animals, reduction of immunoreactive phospho (S473)-Akt was noted throughout the brain. Akt is a key molecule in the insulin/insulin-like growth factor signal transduction pathway, which plays a critical role in the balance between survival and apoptosis. The data presented here raise the possibility that down-regulation of Akt phosphorylation plays a regulatory role in hibernation. This would resemble dauer larva formation in Caenorhabditis elegans where Akt inhibition is associated with energy conservation, fat storage, expression of antioxidant enzymes and growth arrest.
哺乳动物的冬眠是一种可逆的假死状态，与耐受核心体温和新陈代谢的致命性降低有关。冬眠的一个重要方面是耐受脑灌注的显著减少。确定控制地松鼠冬眠的调节机制可以指导开发改善中风和脑外伤治疗方法的努力。在本研究中，我们在多个组织中发现，在冬眠期间，13条纹地松鼠（Spermophilus tridecemlineatus）中Akt（蛋白激酶B）的S473磷酸化显著降低（P<0.001），其激酶活性也显著降低（P=0.023），Akt是一种磷脂酰肌醇-3激酶调节的丝氨酸/苏氨酸激酶。Akt的T308磷酸化相对保持。脑免疫组织化学染色证实了这些结果。在冬眠动物中，整个大脑中免疫反应性磷酸化（S473）-Akt减少。Akt是胰岛素/胰岛素样生长因子信号转导途径中的关键分子，在生存和凋亡之间的平衡中起关键作用。此处呈现的数据提出了Akt磷酸化下调在冬眠中起调节作用的可能性。这类似于秀丽隐杆线虫中 dauer 幼虫的形成，其中Akt抑制与能量保存、脂肪储存、抗氧化酶表达和生长停滞有关。
