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 1mM 4-PBA for 24, 48 or 72h. 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.
Keywords: 4-PBA; GLUT4; Glucose uptake; Hexokinase; L6 myotubes; Reactive oxygen species.
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