Propionate hampers differentiation and modifies histone propionylation and acetylation in skeletal muscle cells. (June 2021)

• Record Type: Journal Article
• Authors: Lagerwaard, Bart; van der Hoek, Marjanne D.; Hoeks, Joris; Grevendonk, Lotte; Nieuwenhuizen, Arie G.; Keijer, Jaap; de Boer, Vincent C.J.
• Is Part Of: Mechanisms of ageing and development. Volume 196(2021)
• Publication Date: 2021-06
• Subjects: Propionylation -- Skeletal muscle differentiation -- Histone acylation -- Aging; Aging -- Periodicals; Developmental biology -- Periodicals; Aging -- Periodicals; Developmental Biology -- Periodicals; Vieillissement -- Périodiques; Biologie du développement -- Périodiques; Aging; Developmental biology; Periodicals; 612.67
• DOI: 10.1016/j.mad.2021.111495
• Languages: English
• ISSNs: 0047-6374

Abstract

Highlights: Propionate exposure increases in propionylation and impairs differentiation in C2C12 and primary muscle cells. Propionate exposure increases propionylation on regulatory promotor regions of Myod. Intramuscular propionylcarnitine is higher in old compared to young individuals. Propionylation and propionyl-CoA could play a role in skeletal muscle physiology and ageing. Abstract: 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.