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

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.