| First Author | Addinsall AB | Year | 2018 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 315 |
| Issue | 2 | Pages | R380-R396 |
| PubMed ID | 29668323 | Mgi Jnum | J:264254 |
| Mgi Id | MGI:6195361 | Doi | 10.1152/ajpregu.00244.2017 |
| Citation | Addinsall AB, et al. (2018) Deficiency of selenoprotein S, an endoplasmic reticulum resident oxidoreductase, impairs the contractile function of fast-twitch hindlimb muscles. Am J Physiol Regul Integr Comp Physiol 315(2):R380-R396 |
| abstractText | 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. |
