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4-Phenyl butyric acid increases particulate hexokinase activity and protects against ROS injury in L6 myotubes

机译:4-苯基丁酸增加颗粒六酮酶活性,并在L6 myotubes中保护ROS损伤

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摘要

Abstract Hexokinase (HK) is the first enzyme in the glycolytic pathway and is responsible for glucose phosphorylation and fixation into the cell. HK (HK-II) is expressed in skeletal muscle and can be found in the cytosol or bound mitochondria, where it can protect cells against insults such as oxidative stress. 4-Phenyl butyric acid (4-PBA) is a chemical chaperone that inhibits endoplasmic reticulum stress and contributes to the restoring of glucose homeostasis. Aims: Here, we decided to investigate whether HK activity and its interaction with mitochondria could be a target of 4-PBA action. Main methods: L6 myotubes were treated with 1 mM 4-PBA for 24, 48 or 72 h. We evaluated HK activity, glucose and oxygen consumption, gene and protein expression. Key findings: We found that L6 myotubes treated with 4-PBA presented more HK activity in the particulate fraction, increased glucose consumption and augmented Glut4 , Hk2 and Vdac1 mRNA expression. Moreover, 4-PBA prevented the deleterious effect of antimycin-A on HK particulate activity. Significance: Together, these results suggest a new role of 4-PBA in glucose metabolism that includes HK as a potential target of beneficial effect of 4-PBA.
机译:摘要六酮酶(HK)是糖酵解途径中的第一种酶,并负责葡萄糖磷酸化和固定到细胞中。 HK(HK-II)在骨骼肌中表达,可以在细胞溶胶或结合的线粒体中发现,可以保护细胞免受氧化应激等损伤。 4-苯基丁酸(4-PBA)是抑制内质网胁迫的化学伴侣,有助于葡萄糖稳态的恢复。目的:在这里,我们决定调查HK活性及其与线粒体的相互作用是否可能是4-PBA行动的目标。主要方法:L6肌管用1mm 4-PBA处理24,48或72小时。我们评估了香港活动,葡萄糖和氧气消耗,基因和蛋白质表达。主要发现:我们发现用4-PBA处理的L6肌管在颗粒部分中呈现更多的HK活性,增加葡萄糖消耗和增强的Glut4,HK2和Vdac1 mRNA表达。此外,4-PBA阻止了抗霉素-A对香港颗粒活性的有害影响。意义:在一起,这些结果表明4-PBA在葡萄糖代谢中的新作用,包括香港作为4-PBA的有益效果的潜在目标。

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