AMPK系统让大脑在能量短缺时“自保”
Sciencedaily · 2011/10/19
利兹、爱丁堡和邓迪大学的研究人员揭示了脑在饥饿状态下的自我保护机制。这一发现有助于治疗那些中风发病风险的病人,因为他们大脑所需的能量在血管供应过程中受到抑制。

利兹大学、爱丁堡大学和丹地大学的研究人员揭示了脑在饥饿状态下的自我保护机制。这一发现有助于治疗那些具有中风发病风险的病人,因为他们大脑所需的能量在血管供应过程中受到抑制。

大脑中许多区域持续消耗的能量等同于马拉松赛跑中大腿肌肉的消耗量。即便处于睡眠状态下,大脑还是需要常规能量。

AMPK系统让大脑在能量限制时进行“自保”

大部分的能量用于激发动作电位,这一微小的电脉冲在大脑中沿着神经元传递。电脉冲在神经元末端可激发化学信号的释放,让大脑处理信息和控制身体机能。

通常情况下,血液向大脑供应充足的葡萄糖和氧气,用于满足动作电位激发所需的大量能量。但是,如果通向大脑的血管变得狭窄或阻塞,关键养分的供应受到限制,故障便可出现。

Chris Peers、Mark Evans和 Grahame Hardie 3位教授共同领导的研究小组发现了大脑在能量供应急缺时的自我保护方式。这一保护策略由AMPK蛋白开启,降低电脉冲的激发频率,用于节约能量。

Graham Hardie教授首次发现了能量感受蛋白AMPK,他说:“早在20世纪80年代,我们对肝脏中脂肪代谢进行研究并发现AMPK系统,但没想到它会在其它器官执行完全不同的功能,比如说大脑中的神经传导。”

市场上目前有刺激AMPK的药物,将来,这些药物连同其它药物能让高危病人更好地应对中风。

Chris Peers教授称:“新研究表明,如果缺少能量,大脑细胞会切换到较慢的工作模式。从长期上看,这一发现很可能形成新的治疗方案,用于解决大脑血液循环问题,从而预防高危人群罹患中风。”

研究的全部细节将发表在《Proceedings of the National Academy of Sciences》期刊上。(生物探索译 Pobee)

 

相关英文论文摘要:

Phosphorylation of the voltage-gated potassium channel Kv2 :1 by AMP-activated protein kinase

Firing of action potentials in excitable cells accelerates ATP turnover. The voltage-gated potassium channel Kv2.1 regulates action potential frequency in central neurons, whereas the ubiquitous cellular energy sensor AMP-activated protein kinase (AMPK) is activated by ATP depletion and protects cells by switching off energy-consuming processes. We show that treatment of HEK293 cells expressing Kv2.1 with the AMPK activator A-769662 caused hyperpolarizing shifts in the current–voltage relationship for channel activation and inactivation. We identified two sites (S440 and S537) directly phosphorylated on Kv2.1 by AMPK and, using phosphospecific antibodies and quantitative mass spectrometry, show that phosphorylation of both sites increased in A-769662–treated cells. Effects of A-769662 were abolished in cells expressing Kv2.1 with S440A but not with S537A substitutions, suggesting that phosphorylation of S440 was responsible for these effects. Identical shifts in voltage gating were observed after introducing into cells, via the patch pipette, recombinant AMPK rendered active but phosphatase-resistant by thiophosphorylation. Ionomycin caused changes in Kv2.1 gating very similar to those caused by A-769662 but acted via a different mechanism involving Kv2.1 dephosphorylation. In cultured rat hippocampal neurons, A-769662 caused hyperpolarizing shifts in voltage gating similar to those in HEK293 cells, effects that were abolished by intracellular dialysis with Kv2.1 antibodies. When active thiophosphorylated AMPK was introduced into cultured neurons via the patch pipette, a progressive, time-dependent decrease in the frequency of evoked action potentials was observed. Our results suggest that activation of AMPK in neurons during conditions of metabolic stress exerts a protective role by reducing neuronal excitability and thus conserving energy.

英文论文链接http://www.pnas.org/content/early/2011/10/13/1106201108.abstract

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