Taniguchi Makoto, Okazaki Toshiro
Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan.
Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan; Department of Hematology/Immunology, Faculty of Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan.
Biochim Biophys Acta. 2014 May;1841(5):692-703. doi: 10.1016/j.bbalip.2013.12.003. Epub 2013 Dec 17.
Sphingomyelin constitutes membrane microdomains such as lipid raft, caveolae, and clathrin-coated pits and implicates in the regulation of trans-membrane signaling. On the other hand, sphingomyelin emerges as an important molecule to generate bioactive sphingolipids through ceramide. Sphingomyelin synthase is an enzyme that generates sphingomyelin and diacylglycerol from phosphatidylcholine and ceramide. Although ceramide has a well-known role as a lipid mediator to regulate cell death and survival, the only known biological role of sphingomyelin regulated by sphingomyelin synthases was limited to being a source of bioactive lipids. Here, we describe the basic characters of sphingomyelin synthases and discuss additional roles for sphingomyelin and sphingomyelin synthase in biological functions including cell migration, apoptosis, autophagy, and cell survival/proliferation as well as in human disorders such as cancer and cardiovascular disorders. It is expected that a better understanding of the role of sphingomyelin regulated by sphingomyelin synthase will shed light on new mechanisms in cell biology, physiology and pathology. In the future, novel therapeutic procedures for currently incurable diseases could be developed through modifying the function of not only sphingolipids, such as sphingomyelin and ceramide, but also of their regulatory enzymes. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology.
鞘磷脂构成膜微结构域，如脂筏、小窝和网格蛋白包被小窝，并参与跨膜信号传导的调节。另一方面，鞘磷脂作为一种重要分子，可通过神经酰胺生成生物活性鞘脂。鞘磷脂合酶是一种从磷脂酰胆碱和神经酰胺生成鞘磷脂和二酰甘油的酶。尽管神经酰胺作为一种脂质介质在调节细胞死亡和存活方面具有众所周知的作用，但由鞘磷脂合酶调节的鞘磷脂唯一已知的生物学作用仅限于作为生物活性脂质的来源。在此，我们描述了鞘磷脂合酶的基本特性，并讨论了鞘磷脂和鞘磷脂合酶在包括细胞迁移、凋亡、自噬以及细胞存活/增殖等生物学功能中，以及在癌症和心血管疾病等人类疾病中的其他作用。预计对由鞘磷脂合酶调节的鞘磷脂作用的更好理解将为细胞生物学、生理学和病理学中的新机制提供线索。未来，通过改变不仅鞘脂（如鞘磷脂和神经酰胺）及其调节酶的功能，可能开发出针对目前无法治愈疾病的新型治疗方法。本文是名为“鞘脂生物学新前沿”的特刊的一部分。
