Is Upregulation of Sarcolipin Beneficial or Detrimental to Muscle Function?
Is Upregulation of Sarcolipin Beneficial or Detrimental to Muscle Function?
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DOI：
10.3389/fphys.2021.633058
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发表时间：
2021
影响因子：
4
通讯作者：
Periasamy M
中科院分区：
文献类型：
--
作者：
Bal NC;Gupta SC;Pant M;Sopariwala DH;Gonzalez-Escobedo G;Turner J;Gunn JS;Pierson CR;Harper SQ;Rafael-Fortney JA;Periasamy M
肌磷脂（Sarcolipin，SLN）是肌浆网Ca ~（2+）-ATP酶（SERCA）泵的调节剂，参与肌肉非颤抖性产热（NST）和能量代谢。有趣的是，SLN表达在肌肉发育期间和几种疾病状态中都显著上调。然而，SLN表达改变在肌肉病理生理学中的意义还不完全清楚。我们先前已经证明，转基因SLN在骨骼肌中的过度表达是无害的，并且可以促进氧化代谢和运动能力。相反，一些研究表明，疾病状态下SLN上调对肌肉功能有害，SLN消融可能是有益的。在这篇前瞻性文章中，我们严格审查了已发表的和一些新的数据，以确定SLN表达与疾病病理学的相关性。本文提出的新数据表明，在全身性细菌（沙门氏菌）感染或脂多糖（LPS）治疗期间，肌肉中的SLN水平被诱导。我们还提出的数据显示，SLN的表达显着上调，在不同类型的肌营养不良症，包括肌管性肌病。这些数据一起揭示了肌肉疾病中SLN表达的上调是进行性的，并且随着严重程度而增加。因此，我们认为SLN表达增加不应被视为疾病的原因;相反，它是一种补偿反应，以满足肌肉更高的能量需求。我们解释说，较高的SLN/SERCA比例积极调节胞质Ca 2+信号通路，以促进线粒体生物合成和氧化代谢，以满足肌肉更高的能量需求。
Sarcolipin (SLN) is a regulator of sarco/endo plasmic reticulum Ca2+-ATPase (SERCA) pump and has been shown to be involved in muscle nonshivering thermogenesis (NST) and energy metabolism. Interestingly, SLN expression is significantly upregulated both during muscle development and in several disease states. However, the significance of altered SLN expression in muscle patho-physiology is not completely understood. We have previously shown that transgenic over-expression of SLN in skeletal muscle is not detrimental, and can promote oxidative metabolism and exercise capacity. In contrast, some studies have suggested that SLN upregulation in disease states is deleterious for muscle function and ablation of SLN can be beneficial. In this perspective article, we critically examine both published and some new data to determine the relevance of SLN expression to disease pathology. The new data presented in this paper show that SLN levels are induced in muscle during systemic bacterial (Salmonella) infection or lipopolysaccharides (LPS) treatment. We also present data showing that SLN expression is significantly upregulated in different types of muscular dystrophies including myotubular myopathy. These data taken together reveal that upregulation of SLN expression in muscle disease is progressive and increases with severity. Therefore, we suggest that increased SLN expression should not be viewed as the cause of the disease; rather, it is a compensatory response to meet the higher energy demand of the muscle. We interpret that higher SLN/SERCA ratio positively modulate cytosolic Ca2+ signaling pathways to promote mitochondrial biogenesis and oxidative metabolism to meet higher energy demand in muscle.
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影响因子：
4.8
作者：
Bombardier, Eric;Smith, Ian C.;Tupling, A. Russell
通讯作者：
Tupling, A. Russell
DOI：
10.1152/ajpcell.1995.269.4.c955
发表时间：
1995-10-01
影响因子：
5.5
作者：
DUMONTEIL, E;BARRE, H;MEISSNER, G
通讯作者：
MEISSNER, G
影响因子：
64.8
作者：
Enerback, S;Jacobsson, A;Kozak, LP
通讯作者：
Kozak, LP
影响因子：
3.9
作者：
Crichton PG;Lee Y;Kunji ER
通讯作者：
Kunji ER
DOI：
10.1073/pnas.0707722104
发表时间：
2007-11-06
影响因子：
11.1
作者：
Babu, Gopal J.;Bhupathy, Poornima;Periasamy, Muthu
通讯作者：
Periasamy, Muthu