Impaired exercise performance is independent of inflammation and cellular stress following genetic reduction or deletion of selenoprotein S
Impaired exercise performance is independent of inflammation and cellular stress following genetic reduction or deletion of selenoprotein S
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DOI：
10.1152/ajpregu.00321.2019
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发表时间：
2020-05-01
影响因子：
2.8
通讯作者：
Stupka, Nicole
中科院分区：
文献类型：
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作者：
Addinsall, Alex Bernard;Wright, Craig Robert;Stupka, Nicole
硒蛋白S（Seps 1）可以保护氧化，内质网（ER）和炎症应激。Seps 1全基因敲除小鼠活动较少，具有受损的快速肌肉离体强度，并且根据上下文，炎症加剧。氧化剂ER和炎症应激调节收缩功能;因此，我们的目的是研究Seps 1基因剂量对运动表现的影响。Seps 1（-/-）基因敲除、Seps 1（-/+）杂合子和野生型小鼠被随机分为3天递增、高强度跑步机跑步或久坐对照组。第4天，测定胫骨前快肌（TA）的原位收缩功能。Seps 1减少或删除损害了运动能力。减少距离。TA强度也降低。在久坐的Seps 1（-/-）基因敲除小鼠中，TA疲劳性大于野生型小鼠，并且通过运动改善。然而，在Seps 1（-/）（+）杂合子小鼠中，运动损害了TA耐力。这些运动能力和TA收缩功能的损害与炎症增加或氧化还原状态失调无关。Seps 1在肌肉纤维和血管中高度表达。有趣的是，在Seps 1（-/-）敲除和Seps 1（-/+）杂合小鼠的TA肌肉中，Nos 1和Vegfa mRNA转录物减少。Seps 1减少或缺失导致的运动表现受损不能归因于细胞应激增强，但可能部分是由细胞应激介导的。Seps 1对微血管的影响。
Selenoprotein S (Seps1) can be protective against oxidative, endoplasmic reticulum (ER), and inflammatory stress. Seps1 global knockout mice are less active, possess compromised fast muscle ex vivo strength, and, depending on context, heightened inflammation. Oxidative. ER, and inflammatory stress modulates contractile function; hence, our aim was to investigate the effects of Seps1 gene dose on exercise performance. Seps1(-/-) knockout, Seps1(-/+) heterozygous, and wild-type mice were randomized to 3 days of incremental, high-intensity treadmill running or a sedentary control group. On day 4, the in situ contractile function of fast tibialis anterior (TA) muscles was determined. Seps1 reduction or deletion compromised exercise capacity. decreasing distance run. TA strength was also reduced. In sedentary Seps1(-/-) knockout mice, TA fatigability was greater than wild-type mice, and this was ameliorated with exercise. Whereas, in Seps1(-/)(+) heterozygous mice, exercise compromised TA endurance. These impairments in exercise capacity and TA contractile function were not associated with increased inflammation or a dysregulated redox state. Seps1 is highly expressed in muscle fibers and blood vessels. Interestingly, Nos1 and Vegfa mRNA transcripts were decreased in TA muscles from Seps1(-/-) knockout and Seps1(-/+) heterozygous mice. Impaired exercise performance with Seps1 reduction or deletion cannot be attributed to heightened cellular stress, but it may potentially be mediated, in part. by the effects of Seps1 on the microvas-culature.