氧氣和葡萄糖是大腦的食物,，如果缺少它們（例如中風(fēng)期間），神經(jīng)細(xì)胞將會(huì)死亡,。一個(gè)由柏林夏洛蒂醫(yī)科大學(xué)和加拿大麥克馬斯特大學(xué)組成的國際研究小組發(fā)現(xiàn)了一種防止細(xì)胞死亡的新機(jī)制,。研究結(jié)果發(fā)表于《美國國家科學(xué)院報(bào)》（PNAS）上。
短暫的缺氧可以作為對(duì)人體細(xì)胞的一個(gè)培訓(xùn),。結(jié)果,，它們?cè)诟L時(shí)間的缺氧情況下能生存的更好--可以這么說,，它們已經(jīng)"準(zhǔn)備好了"。此外,，現(xiàn)在已經(jīng)知道氧氣不足也影響著糖代謝,。然而，到目前為止,，糖代謝和細(xì)胞程序性死亡一直被視為相互獨(dú)立的事件,。
在夏洛蒂醫(yī)科大學(xué)NeuroCure一起工作的2位科學(xué)家Philipp Mergenthaler和Andreas Meisel領(lǐng)導(dǎo)的研究小組現(xiàn)在解釋了這兩個(gè)過程之間的聯(lián)系,。（備注：NeuroCure是夏洛蒂醫(yī)科大學(xué)成立的一個(gè)跨學(xué)科研究聯(lián)盟,，致力于神經(jīng)科學(xué)研究，由德國聯(lián)邦和州政府資助,。）
細(xì)胞的存活由糖代謝中的一個(gè)關(guān)鍵酶（即所謂的己糖激酶-2,，hexokinase-2）調(diào)控，這種酶以一種細(xì)胞可處理的方式改變了葡萄糖,。研究人員發(fā)現(xiàn),，在大腦缺氧的神經(jīng)細(xì)胞中己糖激酶-2被激活了。當(dāng)人中風(fēng)（一種腦部血液循環(huán)障礙）時(shí)便會(huì)出現(xiàn)這種情況,，結(jié)果導(dǎo)致大腦氧氣和養(yǎng)分供應(yīng)不足,，己糖激酶-2隨后發(fā)揮了一種保護(hù)作用。"這種神經(jīng)細(xì)胞的自我保護(hù)作用呈現(xiàn)了一個(gè)重要的基礎(chǔ)機(jī)制,，對(duì)這個(gè)機(jī)制進(jìn)行深入研究可能開發(fā)出一些優(yōu)化的中風(fēng)療法,，"Meisel說。
然而,，缺氧和細(xì)胞代謝改變的分子機(jī)制不僅在中風(fēng)中發(fā)揮作用,，在腫瘤的發(fā)展和免疫系統(tǒng)對(duì)抗感染的防御中同樣非常重要。相應(yīng)地,，這種酶在惡性腫瘤中負(fù)責(zé)糖代謝的改變,。可是,，如果在葡萄糖供應(yīng)不足而氧供應(yīng)正常,，也能夠?qū)е录?xì)胞的死亡。"了解糖代謝是如何調(diào)節(jié)細(xì)胞死亡的基礎(chǔ)機(jī)制從而可能被用來防治中風(fēng),，也可用于選擇性地引起惡性腫瘤細(xì)胞的死亡,，"Mergenthaler解釋道。糖代謝調(diào)節(jié)細(xì)胞死亡的機(jī)制從根本上擴(kuò)大了許多疾病的基本醫(yī)療知識(shí),。（生物谷bioon.com）
doi:10.1073/pnas.1108225109
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Mitochondrial hexokinase II (HKII) and phosphoprotein enriched in astrocytes (PEA15) form a molecular switch governing cellular fate depending on the metabolic state
P. Mergenthaler, A. Kahl, A. Kamitz, V. van Laak, K. Stohlmann, S. Thomsen, H. Klawitter, I. Przesdzing, L. Neeb, D. Freyer, J. Priller, T. J. Collins, D. Megow, U. Dirnagl, D. W. Andrews, A. Meisel
Abstract：The metabolic state of a cell is a key determinant in the decision to live and proliferate or to die. Consequently, balanced energy metabolism and the regulation of apoptosis are critical for the development and maintenance of differentiated organisms. Hypoxia occurs physiologically during development or exercise and pathologically in vascular disease, tumorigenesis, and inflammation, interfering with homeostatic metabolism. Here, we show that the hypoxia-inducible factor (HIF)-1–regulated glycolytic enzyme hexokinase II (HKII) acts as a molecular switch that determines cellular fate by regulating both cytoprotection and induction of apoptosis based on the metabolic state. We provide evidence for a direct molecular interactor of HKII and show that, together with phosphoprotein enriched in astrocytes (PEA15), HKII inhibits apoptosis after hypoxia. In contrast, HKII accelerates apoptosis in the absence of PEA15 and under glucose deprivation. HKII both protects cells from death during hypoxia and functions as a sensor of glucose availability during normoxia, inducing apoptosis in response to glucose depletion. Thus, HKII-mediated apoptosis may represent an evolutionarily conserved altruistic mechanism to eliminate cells during metabolic stress to the advantage of a multicellular organism.
