Glucosylceramide synthase and glycosphingolipid synthesis

Ichikawa, Shinichi; Hirabayashi, Yoshio

doi:10.1016/s0962-8924(98)01249-5

Cited by 209 publications

(184 citation statements)

References 36 publications

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“…Most recent studies show that cholesterol can also be modified with glucose (36). These glycosylated lipids play significant roles in a variety of biological processes, including cellular proliferation, development, differentiation, and stress responses (35,37). Thus, we expected that PhGlc might also have potential roles in mammalian cells.…”

Section: Discussionmentioning

confidence: 99%

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Carbohydrate-dependent signaling from the phosphatidylglucoside-based microdomain induces granulocytic differentiation of HL60 cells

Nagatsuka

Miki

Kasama

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Section: Discussionmentioning

confidence: 99%

“…As a typical example, ceramide is modified with glucose and galactose to form GlcCer and GalCer, respectively (35). Diacylglycerol is glycosylated to form galactosyldiacylglycerol.…”

Section: Discussionmentioning

confidence: 99%

Carbohydrate-dependent signaling from the phosphatidylglucoside-based microdomain induces granulocytic differentiation of HL60 cells

Nagatsuka

Miki

Kasama

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…Glycosylation of ceramide inactivates the molecule's negative growth effects and thus glycosylation may serve as a mechanism for the cell to tolerate excess ceramide levels. 74 Supporting this notion, an association has been found between multidrug resistance and glycosylceramide levels in breast cancer cell lines. 75 Ceramide activates protein kinases that are associated with stress signaling pathways Ceramide-induced apoptosis often involves the SAPK/JNK signaling pathway.…”

Section: Other Molecules Involved In Ceramide Biosynthesis Regulate Cmentioning

confidence: 89%

Ceramide regulates cellular homeostasis via diverse stress signaling pathways

2001

Leukemia

172

111

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The sphingolipid ceramide is an important second signal molecule that regulates diverse signaling pathways involving apoptosis, cell senescence, the cell cycle, and differentiation. For the most part, ceramide's effects are antagonistic to growth and survival. Interestingly, ceramide and the pro-growth agonist, diacylglycerol (DAG) appear to be regulated simultaneously but in opposite directions in the sphingomyelin cycle. While ceramide stimulates signal transduction pathways that are associated with cell death or at least are inhibitory to cell growth (eg stress-activated protein kinase, SAPK, pathways), DAG activates the classical and novel isoforms of the protein kinase C (PKC) family. These PKC isoforms are associated with cell growth and cell survival.

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“…The structure of the enzyme is quite unique since all other glycosyltransferases involved in GSL synthesis are localized to the lumenal side of the Golgi apparatus or ER [45]. It catalyzes the transfer of a glucose moiety from UDP-glucose to the primary hydroxyl group of ceramide to yield GlcCer with inversion of the anomeric configuration for synthesis of glucosylceramide [46][47][48].…”

Section: Structure and Functions Of Glucosylceramide Synthase And Glumentioning

confidence: 99%

“…GCS regulates the balance between ceramide and GlcCer, meaning that GCS regulates drug sensitivity or resistance to anticancer drugs [46]. Intracellular accumulation of ceramide or exogenous ceramides cause anti-proliferative responses, since ceramide is a strong apoptotic molecule [51].…”

Section: Glucosylceramide Synthase In Cancer Therapymentioning

confidence: 99%

Therapeutic potential of targeting ceramide/glucosylceramide pathway in cancer

Yandım

Apohan

Baran

2012

Cancer Chemother Pharmacol

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Sphingolipids including ceramides and its derivatives such as ceramide-1-phosphate, glucosylceramide (GlcCer), and sphingosine-1-phosphate are essential structural components of cell membranes. They now recognized as novel bioeffector molecules which control various aspects of cell growth, proliferation, apoptosis, and drug resistance. Ceramide, the central molecule of sphingolipid metabolism, generally mediates anti-proliferative responses such as inhibition of cell growth, induction of apoptosis, and/or modulation of senescence. There are two major classes of sphingolipids. One of them is glycosphingolipids which are synthesized from the hydrophobic molecule, ceramide. GlcCer, generated by glucosylceramide synthase (GCS) that transfers the glucose from UDPglucose to ceramide, is an important glycosphingolipid metabolic intermediate. GCS regulates the balance between apoptotic ceramide and antiapoptotic GlcCer. Downregulation or inhibition of GCS results in increased apoptosis and decreased drug resistance. The mechanism underlying the drug resistance which develops with increased glucosylceramide expression is associated with P-glycoprotein. In various types of cancers, overexpression of GCS has been observed which renders GCS a good target for the treatment of cancer. This review summarizes our current knowledge on the structure and functions of glucosylceramide synthase and glucosylceramide and on the roles of glucosylceramide synthase in cancer therapy and drug resistance.

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Glucosylceramide synthase and glycosphingolipid synthesis

Cited by 209 publications

References 36 publications

Carbohydrate-dependent signaling from the phosphatidylglucoside-based microdomain induces granulocytic differentiation of HL60 cells

Carbohydrate-dependent signaling from the phosphatidylglucoside-based microdomain induces granulocytic differentiation of HL60 cells

Ceramide regulates cellular homeostasis via diverse stress signaling pathways

Therapeutic potential of targeting ceramide/glucosylceramide pathway in cancer

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