Decreased methylglyoxal-mediated protein glycation in the healthy aging mouse model of ectopic expression of UCP1 in skeletal muscle

Journal article


Masania, J., Witjen, P., Keipert, S., Ost, M., Klaus, S., Rabbani, N. and Thornalley, P. J. 2023. Decreased methylglyoxal-mediated protein glycation in the healthy aging mouse model of ectopic expression of UCP1 in skeletal muscle. Redox Biology. 59, pp. 1-10. https://doi.org/10.1016/j.redox.2022.102574
AuthorsMasania, J., Witjen, P., Keipert, S., Ost, M., Klaus, S., Rabbani, N. and Thornalley, P. J.
Abstract

Mice with ectopic expression of uncoupling protein-1 (UCP1) in skeletal muscle exhibit a healthy aging phenotype with increased longevity and resistance to impaired metabolic health. This may be achieved by decreasing protein glycation by the reactive metabolite, methylglyoxal (MG). We investigated protein glycation and oxidative damage in skeletal muscle of mice with UCP1 expression under control of the human skeletal actin promoter (HSA-mUCP1) at aged 12 weeks (young) and 70 weeks (aged). We found both young and aged HSA-mUCP1 mice had decreased advanced glycation endproducts (AGEs) formed from MG, lysine-derived Nε(1-carboxyethyl)lysine (CEL) and arginine-derived hydroimidazolone, MG-H1, whereas protein glycation by glucose forming Nε-fructosyl-lysine (FL) was increased ca. 2-fold, compared to wildtype controls. There were related increases in FL-linked AGEs, Nε-carboxymethyl-lysine (CML) and 3-deoxylglucosone-derived hydroimidazolone 3DG-H, and minor changes in protein oxidative and nitration adducts. In aged HSA-mUCP1 mice, urinary MG-derived AGEs/FL ratio was decreased ca. 60% whereas there was no change in CML/FL ratio – a marker of oxidative damage. This suggests that, normalized for glycemic status, aged HSA-mUCP1 mice had a lower flux of whole body MG-derived AGE exposure compared to wildtype controls. Proteomics analysis of skeletal muscle revealed a shift to increased heat shock proteins and mechanoprotection and repair in muscle of HSA-mUCP1 mice. Decreased MG-derived AGE protein content in healthy aging of aged HSA-mUCP1 mice is therefore likely related to increased proteolysis of MG-modified proteins and proteostasis surveillance of the skeletal muscle proteome. Decreased formation and increased clearance of MG-derived AGEs may be associated with healthy aging.

KeywordsProteomics; Aging; mechanoprotection
Year2023
JournalRedox Biology
Journal citation59, pp. 1-10
PublisherElsevier
ISSN 2213-2317
Digital Object Identifier (DOI)https://doi.org/10.1016/j.redox.2022.102574
Web address (URL)https://www.sciencedirect.com/science/article/pii/S2213231722003469?via%3Dihub
Accepted author manuscript
File Access Level
Open
Publisher's version
License
File Access Level
Open
Output statusPublished
Publication dates
Online06 Dec 2022
Publication process dates
Accepted05 Dec 2022
Deposited26 Apr 2023
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https://repository.derby.ac.uk/item/9y03w/decreased-methylglyoxal-mediated-protein-glycation-in-the-healthy-aging-mouse-model-of-ectopic-expression-of-ucp1-in-skeletal-muscle

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File access level: Open


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License: CC BY 4.0
File access level: Open

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