Fatty Acid Biosynthesis Inhibition Increases Reduction Potential in Neuronal Cells under Hypoxia.
Fatty Acid Biosynthesis Inhibition Increases Reduction Potential in Neuronal Cells under Hypoxia.
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DOI：
10.3389/fnins.2016.00546
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发表时间：
2016
影响因子：
4.3
通讯作者：
Golovko MY
中科院分区：
文献类型：
--
作者：
Brose SA;Golovko SA;Golovko MY
最近，我们报道了一种新的神经元特异性途径，通过增加脂肪酸(FA)的生物合成，然后酯化为脂类来适应低氧。然而，该途径在低氧条件下的生物学作用仍有待阐明。在目前的研究中，我们验证了我们的假设，即激活FA合成保持还原潜力，并减少低氧下神经细胞的乳酸酸中毒。为了解决这一假设，我们测量了FA合成抑制对暴露于常氧和低氧条件下的神经元SH-SY5Y细胞/NAD+和/NADP+比率以及乳酸水平的影响。在低氧条件下，FA合成抑制剂TOFA(抑制乙酰辅酶A羧化酶)和蓝蛋白(抑制FA合成酶)增加/NAD+和/NADP+比率。此外，在常氧和低氧条件下，抑制FA的合成都会增加乳酸，并在低氧条件下引起细胞毒性，但在常氧条件下不引起细胞毒性。这些结果表明，FA可能在低氧条件下作为氢受体，从而支持包括厌氧糖酵解在内的氧化反应。这些发现可能有助于找出一种根本不同的方法来减轻包括中风在内的神经系统中与缺氧相关的病理生理学。
Recently, we have reported a novel neuronal specific pathway for adaptation to hypoxia through increased fatty acid (FA) biosynthesis followed by esterification into lipids. However, the biological role of this pathway under hypoxia remains to be elucidated. In the presented study, we have tested our hypothesis that activation of FA synthesis maintains reduction potential and reduces lactoacidosis in neuronal cells under hypoxia. To address this hypothesis, we measured the effect of FA synthesis inhibition on /NAD+ and /NADP+ ratios, and lactic acid levels in neuronal SH-SY5Y cells exposed to normoxic and hypoxic conditions. FA synthesis inhibitors, TOFA (inhibits Acetyl-CoA carboxylase) and cerulenin (inhibits FA synthase), increased /NAD+ and /NADP+ ratios under hypoxia. Further, FA synthesis inhibition increased lactic acid under both normoxic and hypoxic conditions, and caused cytotoxicity under hypoxia but not normoxia. These results indicate that FA may serve as hydrogen acceptors under hypoxia, thus supporting oxidation reactions including anaerobic glycolysis. These findings may help to identify a radically different approach to attenuate hypoxia related pathophysiology in the nervous system including stroke.
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影响因子：
7.4
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.18632/aging.100339
发表时间：
2011-06
期刊：
Aging
影响因子：
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作者：
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通讯作者：
Verdin E