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Propionate hampers differentiation and modifies histone propionylation and acetylation in skeletal muscle cells
Mechanisms of Ageing and Development ( IF 5.3 ) Pub Date : 2021-04-28 , DOI: 10.1016/j.mad.2021.111495
Bart Lagerwaard 1 , Marjanne D van der Hoek 2 , Joris Hoeks 3 , Lotte Grevendonk 4 , Arie G Nieuwenhuizen 5 , Jaap Keijer 5 , Vincent C J de Boer 5
Affiliation  

Protein acylation via metabolic acyl-CoA intermediates provides a link between cellular metabolism and protein functionality. A process in which acetyl-CoA and acetylation are fine-tuned is during myogenic differentiation. However, the roles of other protein acylations remain unknown. Protein propionylation could be functionally relevant because propionyl-CoA can be derived from the catabolism of amino acids and fatty acids and was shown to decrease during muscle differentiation. We aimed to explore the potential role of protein propionylation in muscle differentiation, by mimicking a pathophysiological situation with high extracellular propionate which increases propionyl-CoA and protein propionylation, rendering it a model to study increased protein propionylation. Exposure to extracellular propionate, but not acetate, impaired myogenic differentiation in C2C12 cells and propionate exposure impaired myogenic differentiation in primary human muscle cells. Impaired differentiation was accompanied by an increase in histone propionylation as well as histone acetylation. Furthermore, chromatin immunoprecipitation showed increased histone propionylation at specific regulatory myogenic differentiation sites of the Myod gene. Intramuscular propionylcarnitine levels are higher in old compared to young males and females, possibly indicating increased propionyl-CoA levels with age. The findings suggest a role for propionylation and propionyl-CoA in regulation of muscle cell differentiation and ageing, possibly via alterations in histone acylation.



中文翻译:

丙酸盐阻碍分化并改变骨骼肌细胞中的组蛋白丙酰化和乙酰化

通过代谢酰基辅酶A中间体的蛋白质酰化提供了细胞代谢和蛋白质功能之间的联系。乙酰辅酶A和乙酰化被微调的过程是在生肌分化过程中。然而,其他蛋白质酰化的作用仍然未知。蛋白质丙酰化可能与功能相关,因为丙酰辅酶 A 可以源自氨基酸和脂肪酸的分解代谢,并且在肌肉分化过程中会减少。我们旨在探索蛋白质丙酰化在肌肉分化中的潜在作用,通过模拟细胞外丙酸含量高的病理生理情况,这会增加丙酰辅酶 A 和蛋白质丙酰化,使其成为研究蛋白质丙酰化增加的模型。暴露于细胞外丙酸盐,而不是醋酸盐,C2C12 细胞的肌源性分化受损和丙酸盐暴露削弱了原代人类肌肉细胞的肌源性分化。分化受损伴随着组蛋白丙酰化和组蛋白乙酰化的增加。此外,染色质免疫沉淀显示 Myod 基因的特定调节性肌源分化位点的组蛋白丙酰化增加。与年轻男性和女性相比,老年人的肌内丙酰肉碱水平更高,这可能表明丙酰辅酶 A 水平随着年龄的增长而增加。研究结果表明丙酰化和丙酰辅酶A在调节肌肉细胞分化和衰老中的作用,可能是通过组蛋白酰化的改变。分化受损伴随着组蛋白丙酰化和组蛋白乙酰化的增加。此外,染色质免疫沉淀显示 Myod 基因的特定调节性肌源分化位点的组蛋白丙酰化增加。与年轻男性和女性相比,老年人的肌内丙酰肉碱水平更高,这可能表明丙酰辅酶 A 水平随着年龄的增长而增加。研究结果表明丙酰化和丙酰辅酶A在调节肌肉细胞分化和衰老中的作用,可能是通过组蛋白酰化的改变。分化受损伴随着组蛋白丙酰化和组蛋白乙酰化的增加。此外,染色质免疫沉淀显示 Myod 基因的特定调节性肌源分化位点的组蛋白丙酰化增加。与年轻男性和女性相比,老年人的肌内丙酰肉碱水平更高,这可能表明丙酰辅酶 A 水平随着年龄的增长而增加。研究结果表明丙酰化和丙酰辅酶A在调节肌肉细胞分化和衰老中的作用,可能是通过组蛋白酰化的改变。与年轻男性和女性相比,老年人的肌内丙酰肉碱水平更高,这可能表明丙酰辅酶 A 水平随着年龄的增长而增加。研究结果表明丙酰化和丙酰辅酶A在调节肌肉细胞分化和衰老中的作用,可能是通过组蛋白酰化的改变。与年轻男性和女性相比,老年人的肌内丙酰肉碱水平更高,这可能表明丙酰辅酶 A 水平随着年龄的增长而增加。研究结果表明丙酰化和丙酰辅酶A在调节肌肉细胞分化和衰老中的作用,可能是通过组蛋白酰化的改变。

更新日期:2021-05-03
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