Hypoxia Resistance Is an Inherent Phenotype of the Mouse Flexor Digitorum Brevis Skeletal Muscle.
Hypoxia Resistance Is an Inherent Phenotype of the Mouse Flexor Digitorum Brevis Skeletal Muscle.
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DOI：
10.1093/function/zqad012
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发表时间：
2023
期刊：
影响因子：
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骨骼肌的各种功能（运动、呼吸、产热等）都需要氧气 (O2) 的存在。氧气生物利用度不足（即缺氧）不利于肌肉功能，在慢性情况下，可能导致肌肉萎缩。事实证明，目前的治疗干预措施对于挽救骨骼肌免受缺氧损伤基本上无效。然而，我们的实验室已经发现哺乳动物的骨骼肌可以在缺氧的环境中保持适当的生理功能。使用体内后肢缺血和离体缺氧暴露的小鼠模型，我们观察到趾短屈肌（FDB）的力产生保持不变，而相比之下，趾长伸肌（EDL）和比目鱼肌的力输出丧失。与其他肌肉不同，我们发现 FDB 表型不依赖于线粒体，这部分解释了耐缺氧性。使用基于发现的方法对肌肉蛋白质组进行了研究，该方法发现，与 EDL 和比目鱼肌相比，FDB 中跨膜葡萄糖转运蛋白 GLUT1 的表达显着更高。通过功能丧失和获得的方法，我们确定 GLUT1 对于 FDB 在缺氧中生存是必需的，但 GLUT1 的过度表达不足以挽救其他骨骼肌免受缺氧损伤。总的来说，数据表明 FDB 对缺氧损伤具有独特的抵抗力。定义解释表型的机制可能会为开发预防缺氧引起的组织损伤的方法提供见解。采用体内后肢缺血和离体缺氧暴露的小鼠模型来证明 FDB 在无氧情况下发挥作用的能力。基于发现的蛋白质组学发现，与缺氧敏感的 EDL 和比目鱼肌相比，FDB 中葡萄糖转运蛋白 GLUT1 的表达显着更高。功能丧失与获得方法表明，GLUT1 对于 FDB 表型是必需的，但不足以挽救其他骨骼肌免受缺氧损伤。
The various functions of skeletal muscle (movement, respiration, thermogenesis, etc.) require the presence of oxygen (O2). Inadequate O2 bioavailability (ie, hypoxia) is detrimental to muscle function and, in chronic cases, can result in muscle wasting. Current therapeutic interventions have proven largely ineffective to rescue skeletal muscle from hypoxic damage. However, our lab has identified a mammalian skeletal muscle that maintains proper physiological function in an environment depleted of O2. Using mouse models of in vivo hindlimb ischemia and ex vivo anoxia exposure, we observed the preservation of force production in the flexor digitorum brevis (FDB), while in contrast the extensor digitorum longus (EDL) and soleus muscles suffered loss of force output. Unlike other muscles, we found that the FDB phenotype is not dependent on mitochondria, which partially explains the hypoxia resistance. Muscle proteomes were interrogated using a discovery-based approach, which identified significantly greater expression of the transmembrane glucose transporter GLUT1 in the FDB as compared to the EDL and soleus. Through loss-and-gain-of-function approaches, we determined that GLUT1 is necessary for the FDB to survive hypoxia, but overexpression of GLUT1 was insufficient to rescue other skeletal muscles from hypoxic damage. Collectively, the data demonstrate that the FDB is uniquely resistant to hypoxic insults. Defining the mechanisms that explain the phenotype may provide insight towards developing approaches for preventing hypoxia-induced tissue damage. Mouse models of in vivo hindlimb ischemia and ex vivo anoxia exposure were employed to demonstrate the ability of the FDB to function without oxygen. Discovery-based proteomics identified significantly higher expression of the glucose transporter GLUT1 in the FDB as compared to the hypoxia-sensitive EDL and soleus muscles. Loss-and-gain-of-function approaches revealed that GLUT1 is necessary for the FDB phenotype, but insufficient to rescue other skeletal muscles from hypoxic damage.
DOI：
10.3390/antiox6040089
发表时间：
2017-11-09
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
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作者：
Eccardt AM;Bell TP;Mattathil L;Prasad R;Kelly SC;Fisher JS
通讯作者：
Fisher JS