S1P lyase in skeletal muscle regeneration and satellite cell activation: exposing the hidden lyase.
S1P lyase in skeletal muscle regeneration and satellite cell activation: exposing the hidden lyase.
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DOI：
10.1016/j.bbalip.2012.06.009
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发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
de la Garza-Rodea AS
中科院分区：
文献类型：
--
作者：
Saba JD;de la Garza-Rodea AS
鞘氨醇-1-磷酸（S1 P）是一种具有生物活性的鞘脂，其作用对于许多生理过程包括血管生成、淋巴细胞运输和发育是必需的。此外，S1 P作为肌肉营养因子，使有效的肌肉再生。这部分是由于S1 P能够激活肌肉修复所需的静止肌肉干细胞，称为卫星细胞（SC）。然而，S1 P激活SC的分子机制尚未得到很好的理解。此外，缺乏利用S1 P信号传导来募集SC以获得治疗益处的策略。S1 P被S1 P裂解酶（SPL）不可逆地分解代谢，SPL是一种高度保守的酶，催化S1 P在碳键C2-3处的裂解，导致十六烯醛和乙醇胺磷酸的形成。SPL通过底物和产物依赖性事件增强细胞凋亡，从而调节细胞对化疗、放疗和缺血的反应。SPL在静止的小鼠骨骼肌中是检测不到的。然而，我们最近发现SPL在骨骼肌损伤后动态上调。SPL上调发生在一个紧密协调的遗传程序的背景下，导致短暂的S1 P信号响应肌肉损伤。S1 P通过鞘氨醇-1-磷酸受体2（S1 P2）/信号转导子和转录激活子3（STAT 3）依赖性途径激活静止的SC，从而促进骨骼肌再生。作为肌营养不良症（MD）模型的Mdx小鼠表现出骨骼肌SPL上调和S1 P缺陷。药理学SPL抑制提高骨骼肌S1 P水平，增强SC募集和改善mdx骨骼肌再生。这些发现揭示了S1 P如何激活SC，并表明SPL抑制可能为肌病提供治疗策略。这篇文章是题为溶血磷脂研究进展的特刊的一部分。
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid whose actions are essential for many physiological processes including angiogenesis, lymphocyte trafficking and development. In addition, S1P serves asamuscle trophic factor that enables efficient muscle regeneration. This is due in part to S1P's ability to activate quiescent muscle stem cells called satellite cells (SCs) that are needed for muscle repair. However, the molecular mechanism by which S1P activates SCs has not been well understood. Further, strategies for harnessing S1P signaling to recruit SCs for therapeutic benefit have been lacking. S1P is irreversibly catabolized by S1P lyase (SPL), a highly conserved enzyme that catalyzes the cleavage of S1P at carbon bond C2–3, resulting in formation of hexadecenal and ethanolamine-phosphate. SPL enhances apoptosis through substrate- and product-dependent events, thereby regulating cellular responses to chemotherapy, radiation and ischemia. SPL is undetectable in resting murine skeletal muscle. However, we recently found that SPL is dynamically upregulated in skeletal muscle after injury. SPL upregulation occurred in the context of a tightly orchestrated genetic program that resulted in a transient S1P signal in response to muscle injury. S1P activated quiescent SCs via a sphingosine-1-phosphate receptor 2 (S1P2)/signal transducer and activator of transcription 3 (STAT3)-dependent pathway, thereby facilitating skeletal muscle regeneration. Mdx mice, which serve as a model for muscular dystrophy (MD), exhibited skeletal muscle SPL upregulation and S1P deficiency. Pharmacological SPL inhibition raised skeletal muscle S1P levels, enhanced SC recruitment and improved mdx skeletal muscle regeneration. These findings reveal how S1P can activate SCs and indicate that SPL suppression may provide a therapeutic strategy for myopathies. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.
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DOI：
10.1084/jem.20102551
发表时间：
2011-06-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bréart B;Ramos-Perez WD;Mendoza A;Salous AK;Gobert M;Huang Y;Adams RH;Lafaille JJ;Escalante-Alcalde D;Morris AJ;Schwab SR
通讯作者：
Schwab SR
影响因子：
4.8
作者：
Ehrhardt, J;Morgan, J
通讯作者：
Morgan, J
影响因子：
4.8
作者：
Donati, C;Meacci, E;Bruni, P
通讯作者：
Bruni, P
影响因子：
2.1
作者：
Evans, Nicholas P.;Misyak, Sarah A.;Robertson, John L.;Bassaganya-Riera, Josep;Grange, Robert W.
通讯作者：
Grange, Robert W.
影响因子：
5.5
作者：
Danieli-Betto, Daniela;Peron, Samantha;Betto, Romeo
通讯作者：
Betto, Romeo