Histone acetyltransferase inhibitors antagonize AMP-activated protein kinase in postmortem glycolysis.
Histone acetyltransferase inhibitors antagonize AMP-activated protein kinase in postmortem glycolysis.
复制标题
组蛋白乙酰转移酶抑制剂在死后糖酵解中拮抗 AMP 激活的蛋白激酶
DOI：
10.5713/ajas.16.0556
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Shen QW
中科院分区：
文献类型：
--
作者：
Li Q;Li Z;Lou A;Wang Z;Zhang D;Shen QW
目的 探讨AMP激活蛋白激酶（AMPK）激活对死后肌肉蛋白质乙酰化和糖酵解的影响，以更好地了解AMPK调节死后糖酵解和肉品质的机制。方法 32只小鼠随机分为4组，腹腔注射5-氨基咪唑-4-甲酰胺1-β-D-呋喃核苷（AICAR，AMPK特异性激活剂）、AICAR和组蛋白乙酰转移酶抑制剂II，或AICAR、曲古抑菌素A（TSA，组蛋白脱乙酰酶I和II抑制剂）和烟酰胺（NAM，Sirt家族抑制剂）脱乙酰酶）。将小鼠安乐死后，在死后0小时、45分钟和24小时收集背最长肌。测量死后肌肉中的 AMPK 活性、蛋白质乙酰化和糖酵解。结果 AICAR 激活 AMPK 显着增加死后肌肉中的糖酵解。同时，死后 45 分钟肌肉中的乙酰化蛋白总量也有所增加。组蛋白乙酰转移酶抑制剂对蛋白质乙酰化的抑制减少了 AMPK 激活，导致死后早期肌肉乙酰化蛋白总量和糖酵解速率增加，而组蛋白脱乙酰酶抑制剂进一步促进蛋白质乙酰化和糖酵解。检测到几条蛋白质带在具有不同糖酵解速率的肌肉中被差异乙酰化。结论 蛋白质乙酰化在死后糖酵解中发挥重要的调节作用。由于 AMPK 介导屠宰前应激对死后糖酵解的影响，因此蛋白质乙酰化可能是生前应激影响死后代谢和肉品质的机制，但确切机制有待阐明。
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. Methods A 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. Results Activation 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. Conclusion Protein 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.