Histone acetyltransferase inhibitors antagonize AMP-activated protein kinase in postmortem glycolysis.

Qiong Li,Qingwu W. Shen,Aihua Lou,Dequan Zhang,Zhenyu Wang,Zhongwen Li

doi:10.5713/ajas.16.0556

Abstract

ObjectiveThe purpose of this study was to investigate the influence of AMP-activated protein kinase (AMPK) activation on protein acetylation and glycolysis in postmortem muscle to better understand the mechanism by which AMPK regulates postmortem glycolysis and meat quality.MethodsA total of 32 mice were randomly assigned to four groups and intraperitoneally injected with 5-Aminoimidazole-4-carboxamide1-β-D-ribofuranoside (AICAR, a specific activator of AMPK), AICAR and histone acetyltransferase inhibitor II, or AICAR, Trichostatin A (TSA, an inhibitor of histone deacetylase I and II) and Nicotinamide (NAM, an inhibitor of the Sirt family deacetylases). After mice were euthanized, the Longissimus dorsi muscle was collected at 0 h, 45 min, and 24 h postmortem. AMPK activity, protein acetylation and glycolysis in postmortem muscle were measured.ResultsActivation of AMPK by AICAR significantly increased glycolysis in postmortem muscle. At the same time, it increased the total acetylated proteins in muscle 45 min postmortem. Inhibition of protein acetylation by histone acetyltransferase inhibitors reduced AMPK activation induced increase in the total acetylated proteins and glycolytic rate in muscle early postmortem, while histone deacetylase inhibitors further promoted protein acetylation and glycolysis. Several bands of proteins were detected to be differentially acetylated in muscle with different glycolytic rates.ConclusionProtein acetylation plays an important regulatory role in postmortem glycolysis. As AMPK mediates the effects of pre-slaughter stress on postmortem glycolysis, protein acetylation is likely a mechanism by which antemortem stress influenced postmortem metabolism and meat quality though the exact mechanism is to be elucidated.

Highlights

Postmortem glycolysis is one of the most important factors determining the quality of meat
For the prevention of PSE meat, it is critical to control the rate of glycolysis in early postmortem muscle, but questions remain regarding the biochemistry of postmortem glycolysis and the molecular mechanisms through which the normal energy metabolism of postmortem muscle is maintained or disrupted by pre-slaughter practices and genetic factors that lead to altered meat quality development
We hypothesize that protein acetylation plays a role in the regulation of glycolytic enzyme activity, and AMPK regulates the reversible acetylation of glycolytic enzymes through its action on histone acetyltransferase (HAT) and/ or HDAC, which in turn regulates the rate of postmortem glycolysis

Summary

Objective

The purpose of this study was to investigate the influence of AMP-activated protein kinase (AMPK) activation on protein acetylation and glycolysis in postmortem muscle to better understand the mechanism by which AMPK regulates postmortem glycolysis and meat quality. The Longissimus dorsi muscle was collected at 0 h, 45 min, and 24 h postmortem. AMPK activity, protein acetylation and glycolysis in postmortem muscle were measured. Results: Activation of AMPK by AICAR significantly increased glycolysis in postmortem muscle. It increased the total acetylated proteins in muscle 45 min postmortem. Inhibition of protein acetylation by histone acetyltransferase inhibitors reduced AMPK activation induced increase in the total acetylated proteins and glycolytic rate in muscle early postmortem, while histone deacetylase inhibitors further promoted protein acetylation and glycolysis.

INTRODUCTION

MATERIALS AND METHODS

RESULTS AND DISCUSSION