Acid ceramidase is a novel factor required for early embryo survival

Eliyahu, Efrat; Park, Jae Ho; Shtraizent, Nataly; He, Xingxing; Schuchman, Edward H.

doi:10.1096/fj.06-7016com

Cited by 97 publications

(80 citation statements)

References 25 publications

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“…Genetic defects in several of these hydrolytic enzymes cause various disorders with lysosomal accumulation of the substrate lipids, a group of disorders termed the sphingolipidoses [41,[90][91][92][93]. Particularly, some of the known sphingolipidoses might closely associate with aberrant metabolisms of ceramide because of defective activities of ceramide generating/degrading enzymes: Farber's disease, Gaucher disease, and Niemann-Pick type A and B diseases are caused by a deficiency of acid ceramidase [94,95], glucocerebrosidase (acid-β-glucosidase) [96][97][98], acid SMase [99,100], respectively. The salvage pathway is one of the routes for controlling cellular levels of ceramide.…”

Section: Sphingolipidosesmentioning

confidence: 99%

The sphingolipid salvage pathway in ceramide metabolism and signaling

Kitatani

Idkowiak‐Baldys

Hannun

2008

Cellular Signalling

527

457

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Sphingolipids are important components of eukaryotic cells, many of which function as bioactive signaling molecules. Of these, ceramide is a central metabolite and plays key roles in a variety of cellular responses, including regulation of cell growth, viability, differentiation, and senescence. Ceramide is composed of the long-chain sphingoid base, sphingosine, in N-linkage to a variety of acyl groups. Sphingosine serves as the product of sphingolipid catabolism, and it is mostly salvaged through re-acylation, resulting in the generation of ceramide or its derivatives. This recycling of sphingosine is termed the "salvage pathway", and recent evidence points to important roles for this pathway in ceramide metabolism and function. A number of enzymes are involved in the salvage pathway, and these include sphingomyelinases, cerebrosidases, ceramidases, and ceramide synthases. Recent studies suggest that the salvage pathway is not only subject to regulation, but it also modulates the formation of ceramide and subsequent ceramide-dependent cellular signals. This review focuses on the salvage pathway in ceramide metabolism, its regulation, its experimental analysis, and emerging biological functions.

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Section: Sphingolipidosesmentioning

confidence: 99%

The sphingolipid salvage pathway in ceramide metabolism and signaling

Kitatani

Idkowiak‐Baldys

Hannun

2008

Cellular Signalling

527

457

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“…The AC-deficient mouse (Asah1 Ϫ / Ϫ ) undergoes apoptotic death at the 2-cell stage (E1; Fig. 4 ) because of excessive ceramide accumulation ( 39,102 ), demonstrating that AC is expressed in the embryo and that ceramide degradation is essential for survival beyond the 2-cell stage (E1) ( 102 ). In addition to increasing ceramide pools, loss of AC activity is thought to concurrently reduce pools of sphingosine and sphingosine-1-phosphate, two lipids known to promote cell growth and differentiation ( 103 ).…”

Section: Disorders Of Ceramide Degradationmentioning

confidence: 99%

Multi-system disorders of glycosphingolipid and ganglioside metabolism

Xu¹,

Barnes²,

Sun³

et al. 2010

Journal of Lipid Research

142

121

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important to a variety of cellular functions. GSLs and gangliosides are synthesized at the endoplasmic reticulum (ER) and are remodeled during transit from cis to trans Golgi by a series of glycosyl-and sialyl-transferases. These are then transported to the intracellular compartments and the plasma membrane where they become enriched in microdomains and membrane bilayers. During plasma membrane turnover, GSLs and gangliosides can be internalized and partially or completely degraded in the endosomal/lysosomal system to sphingosine and free fatty acids that are then transported or fl ipped across late endosomal and lysosomal membranes for recycling or for use as signaling molecules ( 2, 3 ). GSL metabolic pathwaysGSL biosynthesis begins with condensation of serine and palmitoyl-CoA catalyzed by serine-palmitoyltransferase (SPT) on the cytoplasmic face of the ER, leading to de novo biosynthesis of ceramide, the core of GSLs (

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“…Ceramide may also form membrane channels for proteins like cytochrome C, and stabilize membrane rafts (42). The early embryo is resistant to apoptosis, owing to low levels of ceramide (43,44); however, there has been no measurement of ceramide during fertilization.…”

Section: Lipid Signaling Related To Fertilizationmentioning

confidence: 99%

Lipid levels in sperm, eggs, and during fertilization in Xenopus laevis

Petcoff

Holland

Stith

2008

Journal of Lipid Research

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Critical developmental periods, such as fertilization, involve metabolic activation, membrane fusion events such as sperm-egg or plasma membrane-cortical granule merger, and production and hydrolysis of phospholipids. However, there has been no large-scale quantification of phospholipid changes during fertilization. Using an enzymatic assay, traditional FA analysis by TLC and gas chromatography, along with a new method of phospholipid measurement involving HPLC separation and evaporative light-scattering detection, we report lipid levels in eggs, sperm, and during fertilization in Xenopus laevis. Sperm were found to contain different amounts of phospholipids as compared with eggs. During fertilization, total phosphatidylinositol, lysophosphatidylcholine, sphingomyelin, and phosphatidylserine decreased, and ceramide increased, whereas there was no change in phosphatidylcholine, cardiolipin, or phosphatidylethanolamine. FA analysis of phospholipids found numerous changes during fertilization. Because there is an increase in sn-1,2-diacylglycerol at fertilization, the FAs associated with this increase and the source of the increase in this neutral lipid were examined. Finally, activation of phospholipase C, phospholipase D, phospholipase A2, autotoxin, and sphingomyelinase at fertilization is discussed. Major goals of the LIPID Metabolites and Pathways Strategy (LIPID MAPS) are to "separate and detect all of the lipids in a specific cell," "to quantitate each of the lipid metabolites present and determine the changes in their levels," and to study lipid metabolic pathways during biological events (1). Characterizing changes in the lipid composition during defined biological events is part of the concept of "functional lipidomics" (2). These fundamental, descriptive studies will facilitate our understanding of how lipids regulate membrane fluidity and fusion, lipid rafts, the cytoskeleton, kinases, and protein binding to membranes (e.g., 3-5) to induce pleiotropic cellular effects.About 15 years ago, quantification of lipid mass changes during maturation of the oocyte to the fertilizable egg, and during fertilization of the egg by sperm, was begun in Xenopus laevis (6-9). Critical developmental events can be isolated in vitro with this model system, and large numbers of gametes can be obtained to provide sufficient amounts of second messengers and lipids. During fertilization, membrane bending and fusion are associated with the acrosome reaction of sperm (wherein the large sperm acrosome undergoes exocytosis upon interaction with layers that cover the egg), with sperm-egg merger, and with subsequent fertilization events such as cortical granule exocytosis (10, 11). Furthermore, both Xenopus and human eggs are arrested in meiosis II (12).Compared with oocytes, one disadvantage of studying eggs is that they have a short life, much less than the estimated time for lipid precursor incorporation to near equilibrium levels (6, 7). Thus, lipid analysis based on label incorporation or turnover is not reliable, and ...

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Acid ceramidase is a novel factor required for early embryo survival

Cited by 97 publications

References 25 publications

The sphingolipid salvage pathway in ceramide metabolism and signaling

The sphingolipid salvage pathway in ceramide metabolism and signaling

Multi-system disorders of glycosphingolipid and ganglioside metabolism

Lipid levels in sperm, eggs, and during fertilization in Xenopus laevis

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