Da Silva 2017 Life Sci

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da Silva MH, Peçanha FLM, de Oliveira AM, da-Silva WS (2017) 4-Phenyl butyric acid increases particulate hexokinase activity and protects against ROS injury in L6 myotubes. Life Sci 179:98-102.

» PMID: 28483437

da Silva MH, Pecanha FLM, de Oliveira AM, da-Silva WS (2017) Life Sci

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.

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.

Copyright © 2017 Elsevier Inc. All rights reserved. Keywords: 4-PBA, GLUT4, Glucose uptake, Hexokinase, L6 myotubes, Reactive oxygen species, Rat L6 myoblasts Bioblast editor: Kandolf G

Labels: MiParea: Respiration, Pharmacology;toxicology 

Organism: Rat  Tissue;cell: Skeletal muscle, Other cell lines  Preparation: Intact cells 

Coupling state: ROUTINE 

HRR: Oxygraph-2k