Roles and regulation of ketogenesis in cultured astroglia and neurons under hypoxia and hypoglycemia.
Roles and regulation of ketogenesis in cultured astroglia and neurons under hypoxia and hypoglycemia.
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DOI：
10.1177/1759091414550997
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发表时间：
2014-09-11
期刊：
影响因子：
4.7
通讯作者：
Suzuki N
中科院分区：
文献类型：
--
作者：
Takahashi S;Iizumi T;Mashima K;Abe T;Suzuki N
外源性酮体 (KB)、乙酰乙酸 (AA) 和 β-羟基丁酸 (BHB) 在饥饿状态下的神经细胞中充当替代能源底物。本研究检查了缺氧条件下星形胶质细胞的内源生酮能力（有/无葡萄糖）以及 KB 在神经元能量代谢中的可能作用。从 Sprague-Dawley 大鼠中制备培养的神经元和星形胶质细胞。将棕榈酸 (PAL) 和左旋肉碱 (LC) 添加到测定介质中。使用环硫代-NADH 方法测量 4 至 24 小时 AA 和 BHB 的产量。还测量了 [1-14C]PAL 产生的 14C 标记的酸溶产物 (KB) 和 14CO2。使用l-[U-14C]乳酸([14C]LAC)、[1-14C]丙酮酸([14C]PYR)或β-[1-14C]羟基丁酸([14C]BHB)来比较糖酵解终产物与KB的氧化代谢。将一些细胞置于低氧室（1% O2）中。 PAL 和 LC 诱导星形胶质细胞产生比神经元更高的 KB，而 PAL 产生的 CO2 不到星形胶质细胞和神经元中 KB 产生的 5%。 AMP 激活的蛋白激酶激活剂、AICAR 和二甲双胍以及有/无葡萄糖的缺氧增强了星形胶质细胞中 KB 的产生。在缺乏 PAL 和 LC 的缺氧条件下，神经元 KB 的产生增加。在神经元中，缺氧24小时后，[14C]LAC和[14C]PYR氧化减少，而[14C]BHB氧化保持不变。星形胶质细胞通过增强 KB 的产生来应对体外缺血，并且星形胶质细胞产生的源自脂肪酸的 KB 可能代替乳酸作为三羧酸循环的神经元能量底物，因为丙酮酸脱氢酶容易受到缺血的影响。
Exogenous ketone bodies (KBs), acetoacetate (AA), and β-hydroxybutyrate (BHB) act as alternative energy substrates in neural cells under starvation. The present study examined the endogenous ketogenic capacity of astroglia under hypoxia with/without glucose and the possible roles of KBs in neuronal energy metabolism. Cultured neurons and astroglia were prepared from Sprague-Dawley rats. Palmitic acid (PAL) and l-carnitine (LC) were added to the assay medium. The 4- to 24-hr production of AA and BHB was measured using the cyclic thio-NADH method. 14C-labeled acid-soluble products (KBs) and 14CO2 produced from [1-14C]PAL were also measured. l-[U-14C]lactic acid ([14C]LAC), [1-14C]pyruvic acid ([14C]PYR), or β-[1-14C]hydroxybutyric acid ([14C]BHB) was used to compare the oxidative metabolism of the glycolysis end products with that of the KBs. Some cells were placed in a hypoxic chamber (1% O2). PAL and LC induced a higher production of KBs in astroglia than in neurons, while the CO2 production from PAL was less than 5% of the KB production in both astroglia and neurons. KB production in astroglia was augmented by the AMP-activated protein kinase activators, AICAR and metformin, as well as hypoxia with/without glucose. Neuronal KB production increased under hypoxia in the absence of PAL and LC. In neurons, [14C]LAC and [14C]PYR oxidation decreased after 24 hr of hypoxia, while [14C]BHB oxidation was preserved. Astroglia responds to ischemia in vitro by enhancing KB production, and astroglia-produced KBs derived from fatty acid might serve as a neuronal energy substrate for the tricarboxylic acid cycle instead of lactate, as pyruvate dehydrogenase is susceptible to ischemia.
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影响因子：
6.3
作者：
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通讯作者：
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