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Title: Deficiency of selenoprotein S, an endoplasmic reticulum resident oxidoreductase, impairs the contractile function of fast-twitch hindlimb muscles.
Austin Authors: Addinsall, Alex B;Wright, Craig R;Shaw, Chris S;McRae, Natasha L;Forgan, Leonard G;Weng, Chia-Heng;Conlan, Xavier A;Francis, Paul S;Smith, Zoe M;Andrikopoulos, Sofianos;Stupka, Nicole
Affiliation: Centre for Molecular and Medical Research, School of Medicine, Deakin University, Waurn Ponds, Victoria , Australia
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Deakin University, Waurn Ponds, Victoria , Australia
Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Waurn Ponds, Victoria , Australia
Issue Date: 1-Aug-2018
Date: 2018-04-18
Publication information: American journal of physiology. Regulatory, integrative and comparative physiology 2018; 315(2): R380-R396
Abstract: Selenoprotein S (Seps1) is an endoplasmic reticulum (ER) resident antioxidant implicated in ER stress and inflammation. In human vastus lateralis and mouse hindlimb muscles, Seps1 localization and expression were fiber-type specific. In male Seps1+/- heterozygous mice, spontaneous physical activity was reduced compared with wild-type littermates ( d = 1.10, P = 0.029). A similar trend was also observed in Seps1-/- knockout mice ( d = 1.12, P = 0.051). Whole body metabolism, body composition, extensor digitorum longus (EDL), and soleus mass and myofiber diameter were unaffected by genotype. However, in isolated fast EDL muscles from Seps1-/- knockout mice, the force frequency curve (FFC; 1-120 Hz) was shifted downward versus EDL muscles from wild-type littermates ( d = 0.55, P = 0.002), suggestive of reduced strength. During 4 min of intermittent, submaximal (60 Hz) stimulation, the genetic deletion or reduction of Seps1 decreased EDL force production ( d = 0.52, P < 0.001). Furthermore, at the start of the intermittent stimulation protocol, when compared with the 60-Hz stimulation of the FFC, EDL muscles from Seps1-/- knockout or Seps1+/- heterozygous mice produced 10% less force than those from wild-type littermates ( d = 0.31, P < 0.001 and d = 0.39, P = 0.015). This functional impairment was associated with reduced mRNA transcript abundance of thioredoxin-1 ( Trx1), thioredoxin interacting protein ( Txnip), and the ER stress markers Chop and Grp94, whereas, in slow soleus muscles, Seps1 deletion did not compromise contractile function and Trx1 ( d = 1.38, P = 0.012) and Txnip ( d = 1.27, P = 0.025) gene expression was increased. Seps1 is a novel regulator of contractile function and cellular stress responses in fast-twitch muscles.
DOI: 10.1152/ajpregu.00244.2017
ORCID: 0000-0001-9142-0841
Journal: American journal of physiology. Regulatory, integrative and comparative physiology
PubMed URL: 29668323
Type: Journal Article
Subjects: SEPS1
endoplasmic reticulum stress
fast-twitch muscle
selenoprotein S
Appears in Collections:Journal articles

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