da Silva Michele Hinerasky, Peçanha Flavia Letícia Martins, de Oliveira Aline Machado, da-Silva Wagner Seixas
Laboratório de Adaptações Metabólicas, Programa de Bioquímica e Biofísica Celular, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Laboratório de Adaptações Metabólicas, Programa de Bioquímica e Biofísica Celular, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Life Sci. 2017 Jun 15;179:98-102. doi: 10.1016/j.lfs.2017.05.004. Epub 2017 May 6.
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.
Here, we decided to investigate whether HK activity and its interaction with mitochondria could be a target of 4-PBA action.
L6 myotubes were treated with 1mM 4-PBA for 24, 48 or 72h. We evaluated HK activity, glucose and oxygen consumption, gene and protein expression.
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.
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.
己糖激酶（HK）是糖酵解途径中的第一个酶，负责葡萄糖磷酸化并将其固定在细胞内。HK（HK-II）在骨骼肌中表达，可存在于细胞质或结合在线粒体中，在那里它可以保护细胞免受氧化应激等损伤。4-苯基丁酸（4-PBA）是一种化学伴侣，可抑制内质网应激并有助于恢复葡萄糖稳态。
在此，我们决定研究HK活性及其与线粒体的相互作用是否可能是4-PBA作用的靶点。
将L6肌管用1mM 4-PBA处理24、48或72小时。我们评估了HK活性、葡萄糖和氧气消耗、基因和蛋白质表达。
我们发现用4-PBA处理的L6肌管在颗粒部分呈现出更高的HK活性，葡萄糖消耗增加，Glut4、Hk2和Vdac1 mRNA表达增强。此外，4-PBA可防止抗霉素A对HK颗粒活性的有害影响。
总之，这些结果表明4-PBA在葡萄糖代谢中具有新作用，其中HK是4-PBA有益作用的潜在靶点。
