Disturbances in Calcium Homeostasis Promotes Skeletal Muscle Atrophy: Lessons From Ventilator-Induced Diaphragm Wasting.
Disturbances in Calcium Homeostasis Promotes Skeletal Muscle Atrophy: Lessons From Ventilator-Induced Diaphragm Wasting.
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DOI：
10.3389/fphys.2020.615351
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发表时间：
2020
影响因子：
4
通讯作者：
Powers SK
中科院分区：
文献类型：
--
作者：
Hyatt HW;Powers SK
机械通气（MV）通常是呼吸衰竭患者的救生干预措施。不幸的是，MV延长的常见和不期望的后果是发生血管萎缩和收缩功能障碍。这种MV诱导的膈肌无力通常被标记为“呼吸机诱导的膈肌功能障碍”（VIDD）。VIDD是一个重要的临床问题，因为呼吸无力是患者无法脱离MV的主要风险因素;无法将患者从呼吸机支持中移除导致住院时间延长，发病率和死亡率增加。虽然有几个过程有助于VIDD的发展，但很明显，导致蛋白酶快速活化的氧化应激是主要因素。虽然所有主要的蛋白水解系统都可能导致VIDD，但新出现的证据表明，钙激活蛋白酶钙蛋白酶的激活起着必要的作用。这篇综述强调了导致VIDD的信号通路，重点是促进胞浆钙水平升高和随后的膈肌纤维内钙蛋白酶激活的细胞事件。特别是，我们讨论了新出现的证据，增加线粒体产生的活性氧促进氧化的兰尼碱受体/钙释放通道，导致钙释放肌浆网，加速蛋白水解，和VIDD。最后，我们讨论了与长期MV期间膈肌纤维钙稳态紊乱相关的重要和未回答的问题。
Mechanical ventilation (MV) is often a life-saving intervention for patients in respiratory failure. Unfortunately, a common and undesired consequence of prolonged MV is the development of diaphragmatic atrophy and contractile dysfunction. This MV-induced diaphragmatic weakness is commonly labeled “ventilator-induced diaphragm dysfunction” (VIDD). VIDD is an important clinical problem because diaphragmatic weakness is a major risk factor for the failure to wean patients from MV; this inability to remove patients from ventilator support results in prolonged hospitalization and increased morbidity and mortality. Although several processes contribute to the development of VIDD, it is clear that oxidative stress leading to the rapid activation of proteases is a primary contributor. While all major proteolytic systems likely contribute to VIDD, emerging evidence reveals that activation of the calcium-activated protease calpain plays a required role. This review highlights the signaling pathways leading to VIDD with a focus on the cellular events that promote increased cytosolic calcium levels and the subsequent activation of calpain within diaphragm muscle fibers. In particular, we discuss the emerging evidence that increased mitochondrial production of reactive oxygen species promotes oxidation of the ryanodine receptor/calcium release channel, resulting in calcium release from the sarcoplasmic reticulum, accelerated proteolysis, and VIDD. We conclude with a discussion of important and unanswered questions associated with disturbances in calcium homeostasis in diaphragm muscle fibers during prolonged MV.
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影响因子：
3.3
作者：
Falk, D. J.;DeRuisseau, K. C.;Powers, S. K.
通讯作者：
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影响因子：
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Marks, Andrew R.
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影响因子：
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通讯作者：
MARKS, AR
影响因子：
3.3
作者：
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通讯作者：
Powers, SK