糖鞘脂代谢的药理学调节

Pharmacological Modulation of Glycosphingolipid Metabolism.

作者信息

Inokuchi Jin-Ichi, Ode Takashi, Hara-Yokoyama Miki

机构信息

Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan.

Japan Society for the Promotion of Science (JSPS), Tokyo, Japan.

出版信息

Methods Mol Biol. 2018;1804:401-410. doi: 10.1007/978-1-4939-8552-4_19.

DOI:10.1007/978-1-4939-8552-4_19

PMID:29926420

Abstract

The experimental approach to deplete cellular glycosphingolipids (GSLs) with the specific inhibitors of glycosphingolipid biosynthesis has the potential to identify functions of endogenous GSLs. Most GSLs are derived from glucosylceramide (GlcCer). D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) inhibits GIcCer synthase and has been used extensively to study the biological functions of living cells. D-PDMP inhibits mTORC1 activity, which is independent of its inhibitory activity on GlcCer synthase. We also developed an analog of D-PDMP, D-threo-1-phenyl-2-benzyloxycarbonylamino-3-pyrrolidino-1-propanol (D-PBPP) lacking the effect on mTORC1. Here, we summarize the effects of D-PDMP and D-PBPP on the metabolism of GSLs and cell growth.

摘要

利用鞘糖脂生物合成的特异性抑制剂来消耗细胞内鞘糖脂（GSLs）的实验方法，有潜力确定内源性GSLs的功能。大多数GSLs都源自葡萄糖神经酰胺（GlcCer）。D-苏式-1-苯基-2-癸酰氨基-3-吗啉代-1-丙醇（D-PDMP）可抑制GlcCer合酶，并已被广泛用于研究活细胞的生物学功能。D-PDMP抑制mTORC1活性，这与其对GlcCer合酶的抑制活性无关。我们还开发了一种D-PDMP的类似物，即D-苏式-1-苯基-2-苄氧羰基氨基-3-吡咯烷基-1-丙醇（D-PBPP），它对mTORC1没有影响。在此，我们总结了D-PDMP和D-PBPP对GSLs代谢和细胞生长的影响。