Overexpression of NDRG2 in skeletal muscle does not ameliorate the effects of stress in vivo
- 19 June 2020
- journal article
- research article
- Published by Wiley in Experimental Physiology
- Vol. 105 (8), 1326-1338
- https://doi.org/10.1113/ep088620
Abstract
New Findings What is the central question of this study? Do elevated levels of the stress‐response NDRG2 protein protect against fasting and chronic disease in mouse skeletal muscle? What is the main finding and its importance? NDRG2 levels increased in response to fasting and motor neurone disease effects in the tibialis anterior muscle. No alleviation of the stress‐related and proteasomal pathways, mitochondrial dysfunction or muscle mass loss was observed even with further exogenous NDRG2 added indicating that the increased NDRG2 in skeletal muscle is simply a normal adaptive response. Abstract Skeletal muscle mass loss and dysfunction can arise from stress leading to enhanced protein degradation and metabolic impairment. The expression of N‐myc downstream‐regulated gene 2 (NDRG2) is induced in response to different stressors and is protective against the effects of stress in some tissues and cell types. Here, we investigated endogenous NDRG2 response to fasting and chronic disease stress in mice, and whether exogenous NDRG2 overexpression through adeno‐associated viral (AAV) treatment ameliorated skeletal muscle's response to these conditions. Endogenous levels of NDRG2 increased in the tibialis anterior muscle in response to 24 h fasting and with the development of the motor neurone disease, amyotrophic lateral sclerosis, in SOD1G93A transgenic mice. Despite AAV‐induced overexpression and increased expression with fasting, NDRG2 was unable to protect against the activation of proteasomal and stress pathways in response to fasting. Furthermore, NDRG2 was unable to reduce muscle mass loss, mitochondrial dysfunction, and elevated oxidative and endoplasmic reticulum stress levels in SOD1G93A mice. Conversely, elevated NDRG2 levels did not exacerbate these stress responses. Overall, increasing NDRG2 levels may not be a useful therapeutic strategy to alleviate stress‐related disease pathologies in skeletal muscle. This article is protected by copyright. All rights reservedFunding Information
- Deakin University
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