Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase: an enzyme that preferentially regulates metabolism of very long chain ceramides.

Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase: an enzyme that preferentially regulates metabolism of very long chain ceramides. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase: an enzyme that preferentially regulates metabolism of very long chain ceramides. Abstract Text:

Cungui Mao,Ruijuan Xu,Zdzislaw M Szulc,Jacek Bielawski,Kevin P Becker,Alicja Bielawska,Sehamuddin H Galadari,Wei Hu,Lina M Obeid,

Ceramidases deacylate ceramides, important intermediates in the metabolic pathway of sphingolipids. In this study, we report the cloning and characterization of a novel mouse alkaline ceramidase (maCER1) with a highly restricted substrate specificity. maCER1 consists of 287 amino acids, and it has a 28 and 32% identity to the Saccharomyces alkaline ceramidases (YPC1p and YDC1p) and the human alkaline phytoceramidase, respectively. Reverse transcriptase-PCR analysis demonstrated that maCER1 was predominantly expressed in skin. maCER1 was localized to the endoplasmic reticulum as revealed by immunocytochemistry. In vitro biochemical characterization determined that maCER1 hydrolyzed D-erythro-ceramide exclusively but not D-erythro-dihydroceramide or D-ribo-phytoceramide. Similar to other alkaline ceramidases, maCER1 had an alkaline pH optimum of 8.0, and it was activated by Ca2+ but inhibited by Zn2+,Cu2+, and Mn2+. maCER1 was also inhibited by sphingosine, one of its products. Metabolic labeling studies showed that overexpression of maCER1 caused a decrease in the incorporation of radiolabeled dihydrosphingosine into ceramide and complex sphingolipids but led to a concomitant increase in sphingosine-1-P (S1P) in HeLa cells. Mass measurement showed that overexpression of maCER1 selectively lowered the cellular levels of D-erythro-C24:1-ceramide, but not other ceramide species and caused an increase in the levels of S1P. Taken together, these data suggest that maCER1 is a novel alkaline ceramidase with a stringent substrate specificity and that maCER1 is selectively expressed in skin and may have a role in regulating the levels of bioactive lipids ceramide and S1P, as well as complex sphingolipids.

Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase: an enzyme that preferentially regulates metabolism of very long chain ceramides. Publishing Authors By Initials

C Mao,R Xu,ZM Szulc,J Bielawski,KP Becker,A Bielawska,SH Galadari,W Hu,LM Obeid,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: substrate specificity research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: substrate specificity research

PUBMED ID PMID:

MEDLINE DATE:

Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase: an enzyme that preferentially regulates metabolism of very long chain ceramides. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The Journal of biological chemistry

VOLUME: 278

Page Numbers: 31184-91

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 3

MONTH: 06

YEAR: 2003

Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase: an enzyme that preferentially regulates metabolism of very long chain ceramides. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase: an enzyme that preferentially regulates metabolism of very long chain ceramides. Keywords Mesh Terms:

KEYWORDS: Substrate Specificity

MESH TERMS: metabolism

Chemical & Substance for Abstract: Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase: an enzyme that preferentially regulates metabolism of very long chain ceramides. Information

Substance Name: ceramidase

Registry Number: EC 3.5.1.23

Grant and Affiliation Information for Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase: an enzyme that preferentially regulates metabolism of very long chain ceramides.

AFFILIATION: Department of Medicine, Medical University of South Carolina, Charleston 29425, USA. maoc@musc.edu

Country: United States

AGENCY: United States NIGMS

GRANT: GM62887-01

ACRONYM: GM

MEDLINETA: J Biol Chem

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER: AF347023

Number Hits: 0

Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase: an enzyme that preferentially regulates metabolism of very long chain ceramides Related Publications

• A report of pigeon pox in Sudan.
• Biomarkers of folate and vitamin B(12) status in cerebrospinal fluid.
• Cardiac disease in children in Lebanon: the AUB-MC Children's Cardiac Registry experience.
• Carotid bruits and ischemic cerebrovascular disease.
• Ceramidases: regulators of cellular responses mediated by ceramide, sphingosine, and sphingosine-1-phosphate.
• Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase: an enzyme that preferentially regulates metabolism of very long chain ceramides.
• Combination of C(17) sphingoid base homologues and mass spectrometry analysis as a new approach to study sphingolipid metabolism.
• Diverticulitis of the colon at the American University of Beirut Medical Center.
• Dual and distinct roles for sphingosine kinase 1 and sphingosine 1 phosphate in the response to inflammatory stimuli in RAW macrophages.
• ERP57 Membrane Translocation Dictates the Immunogenicity of Tumor Cell Death by Controlling the Membrane Translocation of Calreticulin.
• Experiences with breast carcinoma in Lebanon. (1958-1971).
• Four cases of neuroleptic malignant syndrome.
• Frequency of herpes simplex virus in Syria based on type-specific serological assay.
• If I had . . . gangrene of the toes.
• Long-chain Ceramide Is a Potent Inhibitor of the Mitochondrial Permeability Transition Pore.
• NEPHROPATHY IN ESSENTIAL FAMILIAL HYPERLIPAEMIA.
• NEPHROPATHY SECONDARY TO ESSENTIAL FAMILIAL HYPERLIPEMIA.
• Necessary role for the Lag1p motif in (dihydro)ceramide synthase activity.
• Principles of bioactive lipid signalling: lessons from sphingolipids.
• Sphingosine Kinase 1 Is Up-regulated during Hypoxia in U87MG Glioma Cells: ROLE OF HYPOXIA-INDUCIBLE FACTORS 1 AND 2.
• Sphingosine-1-phosphate receptors: receptor specificity versus functional redundancy.
• Stigma. An aspect of epilepsy not to be ignored.
• Survey of implant training in oral and maxillofacial surgery residency programs in the United States.
• The management of a lump in the breast.
• Yeast sphingolipids: recent developments in understanding biosynthesis, regulation, and function.
• [Myocardial infarction hospital survival. Multicenter study of 201 patients in 1993]
• [Supplementary tooth germs in orthodontics]
• [Thioctic acid in liver diseases]