Alkaline ceramidase 2 is essential for the homeostasis of plasma sphingoid bases and their phosphates

Fang Li; Ruijuan Xu; Benjamin E. Low; Chih Li Lin; Monica Garcia-Barros; Jennifer Schrandt; Izolda Mileva; Ashley Snider; Catherine K. Luo; Xian Cheng Jiang; Ming Song Li; Yusuf A. Hannun; Lina M. Obeid; Michael V. Wiles; Cungui Mao

doi:10.1096/fj.201700445RR

Alkaline ceramidase 2 is essential for the homeostasis of plasma sphingoid bases and their phosphates

Fang Li, Ruijuan Xu, Benjamin E. Low, Chih Li Lin, Monica Garcia-Barros, Jennifer Schrandt, Izolda Mileva, Ashley Snider, Catherine K. Luo, Xian Cheng Jiang, Ming Song Li, Yusuf A. Hannun, Lina M. Obeid, Michael V. Wiles, Cungui Mao

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

Sphingosine-1-phosphate (S1P) plays important roles in cardiovascular development and immunity. S1P is abundant in plasma because erythrocytes - The major source of S1P-lack any S1P-degrading activity; however, much remains unclear about the source of the plasma S1P precursor, sphingosine (SPH), derived mainly from the hydrolysis of ceramides by the action of ceramidases that are encoded by 5 distinct genes, acid ceramidase 1 (ASAH1)/Asah1, ASAH2/Asah2, alkaline ceramidase 1 (ACER1)/Acer1, ACER2/Acer2, and ACER3/Acer3, in humans/ mice. Previous studies have reported that knocking out Asah1 or Asah2 failed to reduce plasma SPH and S1P levels inmice. Inthis study,we showthatknocking outAcer1 orAcer3 alsofailedtoreduce thebloodlevelsofSPHorS1Pin mice. In contrast, knocking out Acer2 from eitherwhole-body or the hematopoietic lineage markedly decreased the blood levels of SPHand S1P in mice.Of interest, knocking out Acer2 fromwhole-body or the hematopoietic lineage also markedly decreased the levels of dihydrosphingosine (dhSPH) and dihydrosphingosine-1-phosphate (dhS1P) inblood.Taken together, these results suggest thatACER2 plays a key role in themaintenance of high plasma levels of sphingoid base-1-phosphates-S1P and dhS1P-by controlling the generation of sphingoid bases-SPH and dhSPH-in hematopoietic cells.

Original language	English (US)
Pages (from-to)	3058-3069
Number of pages	12
Journal	FASEB Journal
Volume	32
Issue number	6
DOIs	https://doi.org/10.1096/fj.201700445RR
State	Published - Jun 2018
Externally published	Yes

Keywords

Erythrocyte
Hematopoietic cell
Plasma
Sphingolipid
Sphingosine-1-phosphate

ASJC Scopus subject areas

Biotechnology
Biochemistry
Molecular Biology
Genetics

Access to Document

10.1096/fj.201700445RR

Cite this

@article{d4de6c066eab4e78bd84e8a98c6c0c35,

title = "Alkaline ceramidase 2 is essential for the homeostasis of plasma sphingoid bases and their phosphates",

abstract = "Sphingosine-1-phosphate (S1P) plays important roles in cardiovascular development and immunity. S1P is abundant in plasma because erythrocytes - The major source of S1P-lack any S1P-degrading activity; however, much remains unclear about the source of the plasma S1P precursor, sphingosine (SPH), derived mainly from the hydrolysis of ceramides by the action of ceramidases that are encoded by 5 distinct genes, acid ceramidase 1 (ASAH1)/Asah1, ASAH2/Asah2, alkaline ceramidase 1 (ACER1)/Acer1, ACER2/Acer2, and ACER3/Acer3, in humans/ mice. Previous studies have reported that knocking out Asah1 or Asah2 failed to reduce plasma SPH and S1P levels inmice. Inthis study,we showthatknocking outAcer1 orAcer3 alsofailedtoreduce thebloodlevelsofSPHorS1Pin mice. In contrast, knocking out Acer2 from eitherwhole-body or the hematopoietic lineage markedly decreased the blood levels of SPHand S1P in mice.Of interest, knocking out Acer2 fromwhole-body or the hematopoietic lineage also markedly decreased the levels of dihydrosphingosine (dhSPH) and dihydrosphingosine-1-phosphate (dhS1P) inblood.Taken together, these results suggest thatACER2 plays a key role in themaintenance of high plasma levels of sphingoid base-1-phosphates-S1P and dhS1P-by controlling the generation of sphingoid bases-SPH and dhSPH-in hematopoietic cells.",

keywords = "Erythrocyte, Hematopoietic cell, Plasma, Sphingolipid, Sphingosine-1-phosphate",

author = "Fang Li and Ruijuan Xu and Low, {Benjamin E.} and Lin, {Chih Li} and Monica Garcia-Barros and Jennifer Schrandt and Izolda Mileva and Ashley Snider and Luo, {Catherine K.} and Jiang, {Xian Cheng} and Li, {Ming Song} and Hannun, {Yusuf A.} and Obeid, {Lina M.} and Wiles, {Michael V.} and Cungui Mao",

note = "Funding Information: The authors thank Peter M. Kutny (Genetic Engineering Technologies, The Jackson Laboratory) for assistance with microinjections, Cindy Avery at the Jackson Laboratory for animal maintenance and genotyping, and Ping Ji (State University of New York at Stony Brook) for assistance with histological analysis. The authors also thank Dr. Ye Chen (Southern Medical University) for assistance with animal studies. This work was supported, in whole or in part, by U.S. National Institutes of Health, National Cancer Institute Grants R01-CA163825 (to C.M.) and P01-CA097132 (to Y.A.H. and C.M.). This work was also supported by the Sphingolipid Animal Cancer Pathobiology Shared Resource Core. The authors declare no conflicts of interest. Publisher Copyright: {\textcopyright} 2018 FASEB.",

year = "2018",

month = jun,

doi = "10.1096/fj.201700445RR",

language = "English (US)",

volume = "32",

pages = "3058--3069",

journal = "FASEB Journal",

issn = "0892-6638",

publisher = "FASEB",

number = "6",

}

TY - JOUR

T1 - Alkaline ceramidase 2 is essential for the homeostasis of plasma sphingoid bases and their phosphates

AU - Li, Fang

AU - Xu, Ruijuan

AU - Low, Benjamin E.

AU - Lin, Chih Li

AU - Garcia-Barros, Monica

AU - Schrandt, Jennifer

AU - Mileva, Izolda

AU - Snider, Ashley

AU - Luo, Catherine K.

AU - Jiang, Xian Cheng

AU - Li, Ming Song

AU - Hannun, Yusuf A.

AU - Obeid, Lina M.

AU - Wiles, Michael V.

AU - Mao, Cungui

N1 - Funding Information: The authors thank Peter M. Kutny (Genetic Engineering Technologies, The Jackson Laboratory) for assistance with microinjections, Cindy Avery at the Jackson Laboratory for animal maintenance and genotyping, and Ping Ji (State University of New York at Stony Brook) for assistance with histological analysis. The authors also thank Dr. Ye Chen (Southern Medical University) for assistance with animal studies. This work was supported, in whole or in part, by U.S. National Institutes of Health, National Cancer Institute Grants R01-CA163825 (to C.M.) and P01-CA097132 (to Y.A.H. and C.M.). This work was also supported by the Sphingolipid Animal Cancer Pathobiology Shared Resource Core. The authors declare no conflicts of interest. Publisher Copyright: © 2018 FASEB.

PY - 2018/6

Y1 - 2018/6

N2 - Sphingosine-1-phosphate (S1P) plays important roles in cardiovascular development and immunity. S1P is abundant in plasma because erythrocytes - The major source of S1P-lack any S1P-degrading activity; however, much remains unclear about the source of the plasma S1P precursor, sphingosine (SPH), derived mainly from the hydrolysis of ceramides by the action of ceramidases that are encoded by 5 distinct genes, acid ceramidase 1 (ASAH1)/Asah1, ASAH2/Asah2, alkaline ceramidase 1 (ACER1)/Acer1, ACER2/Acer2, and ACER3/Acer3, in humans/ mice. Previous studies have reported that knocking out Asah1 or Asah2 failed to reduce plasma SPH and S1P levels inmice. Inthis study,we showthatknocking outAcer1 orAcer3 alsofailedtoreduce thebloodlevelsofSPHorS1Pin mice. In contrast, knocking out Acer2 from eitherwhole-body or the hematopoietic lineage markedly decreased the blood levels of SPHand S1P in mice.Of interest, knocking out Acer2 fromwhole-body or the hematopoietic lineage also markedly decreased the levels of dihydrosphingosine (dhSPH) and dihydrosphingosine-1-phosphate (dhS1P) inblood.Taken together, these results suggest thatACER2 plays a key role in themaintenance of high plasma levels of sphingoid base-1-phosphates-S1P and dhS1P-by controlling the generation of sphingoid bases-SPH and dhSPH-in hematopoietic cells.

AB - Sphingosine-1-phosphate (S1P) plays important roles in cardiovascular development and immunity. S1P is abundant in plasma because erythrocytes - The major source of S1P-lack any S1P-degrading activity; however, much remains unclear about the source of the plasma S1P precursor, sphingosine (SPH), derived mainly from the hydrolysis of ceramides by the action of ceramidases that are encoded by 5 distinct genes, acid ceramidase 1 (ASAH1)/Asah1, ASAH2/Asah2, alkaline ceramidase 1 (ACER1)/Acer1, ACER2/Acer2, and ACER3/Acer3, in humans/ mice. Previous studies have reported that knocking out Asah1 or Asah2 failed to reduce plasma SPH and S1P levels inmice. Inthis study,we showthatknocking outAcer1 orAcer3 alsofailedtoreduce thebloodlevelsofSPHorS1Pin mice. In contrast, knocking out Acer2 from eitherwhole-body or the hematopoietic lineage markedly decreased the blood levels of SPHand S1P in mice.Of interest, knocking out Acer2 fromwhole-body or the hematopoietic lineage also markedly decreased the levels of dihydrosphingosine (dhSPH) and dihydrosphingosine-1-phosphate (dhS1P) inblood.Taken together, these results suggest thatACER2 plays a key role in themaintenance of high plasma levels of sphingoid base-1-phosphates-S1P and dhS1P-by controlling the generation of sphingoid bases-SPH and dhSPH-in hematopoietic cells.

KW - Erythrocyte

KW - Hematopoietic cell

KW - Plasma

KW - Sphingolipid

KW - Sphingosine-1-phosphate

UR - http://www.scopus.com/inward/record.url?scp=85048718809&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048718809&partnerID=8YFLogxK

U2 - 10.1096/fj.201700445RR

DO - 10.1096/fj.201700445RR

M3 - Article

C2 - 29401619

AN - SCOPUS:85048718809

SN - 0892-6638

VL - 32

SP - 3058

EP - 3069

JO - FASEB Journal

JF - FASEB Journal

IS - 6

ER -

Alkaline ceramidase 2 is essential for the homeostasis of plasma sphingoid bases and their phosphates

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this