Carnosine ameliorates dexamethasone-induced muscle atrophy with associated modulation of ubiquitin ligases and oxidative stress in C57BL/6J female mice

TL;DR

Carnosine helps prevent muscle loss caused by dexamethasone in mice by reducing harmful protein activity and oxidative stress.

Contribution

This study shows carnosine can reduce dexamethasone-induced muscle atrophy by targeting ubiquitin ligases and oxidative stress.

Findings

Carnosine mitigated dexamethasone-induced reductions in muscle mass and myofiber cross-sectional area.

Carnosine suppressed the expression of atrophy-related ubiquitin ligases Atrogin-1, MuRF1, and Cbl-b.

Carnosine reduced oxidative stress and preserved IRS-1 levels in dexamethasone-treated mice.

Abstract

Muscle atrophy, characterized by a decline in muscle mass and function, has limited treatment options, highlighting the need for further research. In this study, we investigated the effect of carnosine, a dipeptide with well-established antioxidant properties, on dexamethasone (Dex)-induced muscle atrophy in female C57BL/6J mice. Dex (10 mg/kg body weight) reduced muscle weight, cross-sectional area (CSA), and myosin heavy chain (MyHC) protein expression, while elevating the expression of the muscle atrophy–related ubiquitin ligases Atrogin-1 and Muscle RING-finger protein-1 (MuRF1). Dex also increased oxidative stress, leading to upregulation of the oxidative stress–sensitive ubiquitin ligase Cbl-b and downregulation of IRS-1. Notably, a 21-day treatment with carnosine (300 mg/kg body weight) significantly mitigated Dex-induced reductions in muscle mass, myofiber CSA, and MyHC protein, while suppressing ubiquitin ligase expression and preserving IRS-1 levels. Carnosine likewise decreased oxidative stress and the associated Cbl-b upregulation. These findings suggest that carnosine is a promising therapeutic candidate for managing Dex-induced muscle atrophy.

•
Carnosine prevented dexamethasone-induced muscle atrophy by improving myofiber CSA in mice.
•
Carnosine effectively attenuated Dex-induced degradation of fast and slow MyHC proteins.
•
Carnosine suppressed muscle-atrophy–associated ubiquitin ligases.
•
Carnosine acts as a strong antioxidant and reduces oxidative stress.

Carnosine prevented dexamethasone-induced muscle atrophy by improving myofiber CSA in mice.

Carnosine effectively attenuated Dex-induced degradation of fast and slow MyHC proteins.

Carnosine suppressed muscle-atrophy–associated ubiquitin ligases.

Carnosine acts as a strong antioxidant and reduces oxidative stress.

Figures