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 journalArticlepeer-review

19 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 languageEnglish (US)
Pages (from-to)3058-3069
Number of pages12
JournalFASEB Journal
Volume32
Issue number6
DOIs
StatePublished - Jun 2018
Externally publishedYes

Keywords

  • Erythrocyte
  • Hematopoietic cell
  • Plasma
  • Sphingolipid
  • Sphingosine-1-phosphate

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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