GSK3β Regulates Brain Energy Metabolism.
GSK3β Regulates Brain Energy Metabolism.
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DOI：
10.1016/j.celrep.2018.04.045
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发表时间：
2018-05-15
期刊：
影响因子：
8.8
通讯作者：
Anderson RM
中科院分区：
文献类型：
--
作者：
Martin SA;Souder DC;Miller KN;Clark JP;Sagar AK;Eliceiri KW;Puglielli L;Beasley TM;Anderson RM
GSK 3 β是一种丝氨酸苏氨酸激酶，与阿尔茨海默病的进展有关。尽管GSK 3 β在生长和病理学中的作用已得到广泛研究，但人们对GSK 3 β操纵的代谢后果知之甚少，特别是在大脑中。在这里，我们发现GSK 3 β调节人H4神经胶质瘤细胞和大鼠PC 12衍生神经元细胞的线粒体能量代谢，并且在小鼠体内抑制GSK 3 β以区域特异性方式改变海马的代谢。我们证明，GSK 3 β抑制增加线粒体呼吸和膜电位，并改变NAD（P）H代谢。这些代谢效应与PGC-1α蛋白稳定性增加、核定位增强和转录共激活增加相关。在接受GSK 3 β抑制剂碳酸锂治疗的小鼠中，海马能量代谢的变化与PGC-1α增加有关。这些数据强调了脑GSK 3 β的代谢作用，并表明GSK 3 β/PGC-1α轴可能在神经元代谢完整性中很重要。Martin等人证明GSK 3 β是大脑中能量代谢的调节剂。他们表明，GSK 3 β抑制刺激线粒体调节因子PGC-1α，并导致神经胶质细胞、培养神经元和小鼠体内海马中线粒体和氧化还原途径的激活。
GSK3β is a serine threonine kinase implicated in the progression of Alzheimer’s disease. Although the role of GSK3β in growth and pathology has been extensively studied, little is known about the metabolic consequences of GSK3β manipulation, particularly in the brain. Here, we show that GSK3β regulates mitochondrial energy metabolism in human H4 neuroglioma cells and rat PC12-derived neuronal cells and that inhibition of GSK3β in mice in vivo alters metabolism in the hippocampus in a region-specific manner. We demonstrate that GSK3β inhibition increases mitochondrial respiration and membrane potential and alters NAD(P)H metabolism. These metabolic effects are associated with increased PGC-1α protein stabilization, enhanced nuclear localization, and increased transcriptional co-activation. In mice treated with the GSK3β inhibitor lithium carbonate, changes in hippocampal energy metabolism are linked to increased PGC-1α. These data highlight a metabolic role for brain GSK3β and suggest that the GSK3β/PGC-1α axis may be important in neuronal metabolic integrity. Martin et al. demonstrate that GSK3β is a regulator of energy metabolism in the brain. They show that GSK3β inhibition stimulates mitochondrial regulator PGC-1α and leads to activation of mitochondrial and redox pathways in glia, in neurons in culture, and in the hippocampus in mice in vivo.
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DOI：
10.1126/science.1173635
发表时间：
2009-07-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Colman RJ;Anderson RM;Johnson SC;Kastman EK;Kosmatka KJ;Beasley TM;Allison DB;Cruzen C;Simmons HA;Kemnitz JW;Weindruch R
通讯作者：
Weindruch R
影响因子：
7.8
作者：
Martin SA;DeMuth TM;Miller KN;Pugh TD;Polewski MA;Colman RJ;Eliceiri KW;Beasley TM;Johnson SC;Anderson RM
通讯作者：
Anderson RM
影响因子：
4.8
作者：
Nemoto, S;Fergusson, MM;Finkel, T
通讯作者：
Finkel, T
PGC-1Alpha定位和周转的动态调节暗示卡路里限制和应力反应中的线粒体适应性。
影响因子：
7.8
作者：
Anderson, Rozalyn M.;Barger, Jamie L.;Edwards, Michael G.;Braun, Kristina H.;O'Connor, Clare E.;Prolla, Tomas A.;Weindruch, Richard
通讯作者：
Weindruch, Richard
影响因子：
13.5
作者：
Beurel, Eleonore;Grieco, Steven F.;Jope, Richard S.
通讯作者：
Jope, Richard S.