HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.06-7016comv1 21/7/1403    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Eliyahu, E. Articles by Schuchman, E. H. Search for Related Content PubMed PubMed Citation Articles by Eliyahu, E. Articles by Schuchman, E. H.

Acid ceramidase is a novel factor required for early embryo survival

Department of Human Genetics, Mount Sinai School of Medicine, New York, New York, USA

¹Correspondence: Department of Human Genetics, Mt. Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA. E-mail: edward.schuchman{at}mssm.edu

Recent studies suggest that the lipid, ceramide, induces the default apoptosis process in eggs. Yet, it is obscure how newly formed embryos overcome this fate. Acid ceramidase (AC) is a key regulatory enzyme involved in ceramide metabolism, and mutations in the AC gene (Asah1) result in Farber Lipogranulomatosis, a fatal human genetic disorder. Our previous studies revealed that AC knockout (Asah1–/–) mice had a lethal phenotype, and herein we reveal the mechanism underlying this observation. A single-cell, polymerase chain reaction (PCR) genotyping method was developed to analyze individual embryos from Asah1 ± intercrosses. Combined with Annexin V staining, this genotype analysis demonstrated that Asah1–/– embryos could not survive beyond the 2-cell stage, and underwent apoptotic death. Notably, sphingosine-1-phosphate (S1P) treatment of early 2-cell embryos from the Asah1 ± intercrosses rescued Asah1–/– embryos, and enabled their progression from the 2-cell to 4–8-cell stage. Quantitative PCR also revealed that expression of the Asah1 gene in healthy embryos was initiated at the 2-cell stage, coincident with embryonic genome activation (EGA). AC activity and Western blot analyses further demonstrated high expression and activity of the enzyme in normal, unfertilized eggs, which likely provide the protein to newly formed embryos prior to EGA. Based on these observations, we suggest that AC is an essential factor required for embryo survival that functions by removing ceramide from the newly formed embryos, thus inhibiting the default apoptosis pathway. Eliyahu, E., Park, J.-H., Shtraizent, N., He, X., Schuchman, E. H. Acid ceramidase is a novel factor required for early embryo survival.

Key Words: apoptosis • oocytes • ceramide

This article has been cited by other articles:

				S. Uhlig and E. Gulbins Sphingolipids in the Lungs Am. J. Respir. Crit. Care Med., December 1, 2008; 178(11): 1100 - 1114. [Abstract] [Full Text] [PDF]

				D. W. Petcoff, W. L. Holland, and B. J. Stith Lipid levels in sperm, eggs, and during fertilization in Xenopus laevis J. Lipid Res., November 1, 2008; 49(11): 2365 - 2378. [Abstract] [Full Text] [PDF]

				I. A. Savtchouk, F. J. Mattie, and A. A. Ollis Ceramide: From Embryos to Tumors Sci. Signal., September 2, 2008; 1(35): jc1 - jc1. [Abstract] [Full Text] [PDF]

				X. Ye Lysophospholipid signaling in the function and pathology of the reproductive system Hum. Reprod. Update, September 1, 2008; 14(5): 519 - 536. [Abstract] [Full Text] [PDF]

				N. Shtraizent, E. Eliyahu, J.-H. Park, X. He, R. Shalgi, and E. H. Schuchman Autoproteolytic Cleavage and Activation of Human Acid Ceramidase J. Biol. Chem., April 25, 2008; 283(17): 11253 - 11259. [Abstract] [Full Text] [PDF]

				I. A. Savtchouk, F. J. Mattie, and A. A. Ollis Ceramide: from Embryos to Tumors Sci. Signal., July 10, 2007; 2007(394): jc1 - jc1. [Abstract] [Full Text] [PDF]