Elevation of ceramide in serum lipoproteins during acute phase response in humans and mice: Role of serine-palmitoyl transferase

Sandy Lightle, Raina Tosheva, Amy Lee, Jennie Queen-Baker, Boris Boyanovsky, Steve Shedlofsky, Mariana Nikolova-Karakashian

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Recent studies have indicated that ceramide generated in the liver is secreted into the bloodstream as component of very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). This manuscript investigates the effect of host acute phase response to inflammation on lipoprotein ceramide levels. In humans, two different patterns of responses were found. One group of volunteers experienced transient increases in serum ceramide at 1.5h after LPS administration. Second group showed prolonged increases that reached up to 10-fold above the basal level and continued for up to 24h. Increases in ceramide were found only in VLDL and LDL particles. LPS administration induced similar increases in mice. These increases were accompanied by activation of secreted sphingomyelinase in serum and serine-palmitoyl transferase in liver. ASMase knockout mice retained LPS-induced increases in serum ceramide, thus suggesting that the elevation of VLDL and LDL ceramide content is attributed at least in part to activation of de novo synthesis of ceramide in the liver.

Original languageEnglish
Pages (from-to)120-128
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume419
Issue number2
DOIs
StatePublished - Nov 15 2003

Bibliographical note

Funding Information:
This work was supported partly by research award from the American Federation for Aging Research (to M.N.-K) and a Grant-in-Aid from the American Heart Association (Ohio Valley affiliate (to M.N.-K), as well as by the Department of Veterans Affairs Merit Award Program (to S.I.S.) and by M01RR02602 NIH Grant for the University of Kentucky General Clinical Research Center (to S.I.S.). We greatly appreciate the comments of the Cardiovascular Research Group.

Keywords

  • Atherosclerosis
  • LPS
  • Liver
  • Sphingomyelinase
  • Sphingosine

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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