Fermented Oyster Extract Attenuated Dexamethasone-Induced Muscle Atrophy by Decreasing Oxidative Stress.

Seyeon Oh,Bae-Jin Lee,Kyunghee Byun,Chang Hu Choi,Kuk-Hui Son,Joung-Hyun Park

doi:10.3390/molecules26237128

Abstract

It is well known that oxidative stress induces muscle atrophy, which decreases with the activation of Nrf2/HO-1. Fermented oyster extracts (FO), rich in γ-aminobutyric acid (GABA) and lactate, have shown antioxidative effects. We evaluated whether FO decreased oxidative stress by upregulating Nrf2/HO-1 and whether it decreased NF-κB, leading to decreased IL-6 and TNF-α. Decreased oxidative stress led to the downregulation of Cbl-b ubiquitin ligase, which increased IGF-1 and decreased FoxO3, atrogin1, and Murf1, and eventually decreased muscle atrophy in dexamethasone (Dexa)-induced muscle atrophy animal model. For four weeks, mice were orally administered with FO, GABA, lactate, or GABA+Lactate, and then Dexa was subcutaneously injected for ten days. During Dexa injection period, FO, GABA, lactate, or GABA+Lactate were also administered, and grip strength test and muscle harvesting were performed on the day of the last Dexa injection. We compared the attenuation effect of FO with GABA, lactate, and GABA+lactate treatment. Nrf2 and HO-1 expressions were increased by Dexa but decreased by FO; SOD activity and glutathione levels were decreased by Dexa but increased by FO; NADPH oxidase activity was increased by Dexa but decreased by FO; NF-κB, IL-6, and TNF-α activities were increased by Dexa were decreased by FO; Cbl-b expression was increased by Dexa but restored by FO; IGF-1 expression was decreased by Dexa but increased by FO; FoxO3, Atrogin-1, and MuRF1 expressions were increased by Dexa but decreased by FO. The gastrocnemius thickness and weight were decreased by Dexa but increased by FO. The cross-sectional area of muscle fiber and grip strength were decreased by Dexa but increased by FO. In conclusion, FO decreased Dexa-induced oxidative stress through the upregulation of Nrf2/HO-1. Decreased oxidative stress led to decreased Cbl-b, FoxO3, atrogin1, and MuRF1, which attenuated muscle atrophy.

Highlights

It is known that excessive oxidative stress caused by an imbalance between the generation and removal of intracellular reactive oxygen species (ROS) can decrease protein synthesis and enhance protein degradation, eventually leading to muscle atrophy [1,2,3].Dexamethasone (Dexa) can cause oxidative stress in various cells such as skeletal muscle cells, adipocytes, pancreatic cells, and osteoblastic cells [4,5,6,7,8]
The upregulation of casitas Blineage lymphoma proto-oncogene-b (Cbl-b) by ROS leads to decreased insulin-like growth factor-1 (IGF-1) signaling [9,10], which leads to increased dephosphorylation of Forkhead box O (FoxO) 3a and induces upregulation of muscle atrophy-associated ubiquitin ligases, such as muscle atrophy F-box (MAFbx)/atrogin-1 and muscle RING finger 1 (MuRF1) [11]
In the homeostatic state without oxidative stress, inactivated Nuclear factor erythroid 2-related factor 2 (Nrf2) exists in the cytoplasm by binding to Kelch-like ECH-associated protein 1 (Keap1), which prohibits the nuclear translocation of Nrf2 [12,14,15]

Summary

Introduction

It is known that excessive oxidative stress caused by an imbalance between the generation and removal of intracellular reactive oxygen species (ROS) can decrease protein synthesis and enhance protein degradation, eventually leading to muscle atrophy [1,2,3].Dexamethasone (Dexa) can cause oxidative stress in various cells such as skeletal muscle cells, adipocytes, pancreatic cells, and osteoblastic cells [4,5,6,7,8]. It is known that excessive oxidative stress caused by an imbalance between the generation and removal of intracellular reactive oxygen species (ROS) can decrease protein synthesis and enhance protein degradation, eventually leading to muscle atrophy [1,2,3]. Excessive ROS in rodent myotubes has reportedly enhanced expression of the ubiquitin ligase casitas Blineage lymphoma proto-oncogene-b (Cbl-b), eventually leading to the degradation of insulin receptor substate-1 (IRS-1) which causes muscle atrophy [9]. The upregulation of Cbl-b by ROS leads to decreased insulin-like growth factor-1 (IGF-1) signaling [9,10], which leads to increased dephosphorylation of Forkhead box O (FoxO) 3a and induces upregulation of muscle atrophy-associated ubiquitin ligases, such as muscle atrophy F-box (MAFbx)/atrogin-1 and muscle RING finger 1 (MuRF1) [11].

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Conclusion