Release of ceramide after membrane sphingomyelin hydrolysis decreases the basolateral secretion of triacylglycerol and apolipoprotein B in cultured human intestinal cells

F Jeffrey Field; Heshun Chen; Ella  Born; Brad  Dixon; Satya  Mathur

doi:10.1172/JCI116876

Back

Release of ceramide after membrane sphingomyelin hydrolysis decreases the basolateral secretion of triacylglycerol and apolipoprotein B in cultured human intestinal cells

Journal article

Open access

Peer reviewed

Release of ceramide after membrane sphingomyelin hydrolysis decreases the basolateral secretion of triacylglycerol and apolipoprotein B in cultured human intestinal cells

F Jeffrey Field, Heshun Chen, Ella Born, Brad Dixon and Satya Mathur

The Journal of clinical investigation, Vol.92(6), pp.2609-2619

12/1993

DOI: 10.1172/JCI116876

PMCID: PMC288457

PMID: 8254018

Files and links (1)

url

https://doi.org/10.1172/JCI116876View

Published (Version of record) Open Access

Abstract

The effect of sphingomyelin hydrolysis on triacylglycerol-rich lipoprotein secretion was examined in the human intestinal cell line, CaCo-2. Addition of sphingomyelinase decreased sphingomyelin and phosphatidylethanolamine by 60 and 20%, respectively. Sphingomyelin hydrolysis decreased the basolateral secretion of triacylglycerol mass, newly synthesized triacylglycerol, and apo B mass. Pulse-chase experiments with [35S]methionine demonstrated a decrease in apo B synthesis and a marked decrease in apo B100 and apo B48 secretion without altering apo A1 secretion. Sphingomyelin hydrolysis did not change apo B mRNA levels nor apo B turnover. Phosphatidylcholine-specific phospholipase C did not decrease apo B synthesis or its basolateral secretion. Membrane protein kinase C (PKC) activity was decreased twofold after sphingomyelin hydrolysis. The PKC inhibitor staurosporine decreased apo B mass and newly synthesized apo B secretion. Sphingomyelinase and staurosporine together caused an additional decrease in apo B secretion suggesting that sphingomyelin hydrolysis decreased apo B secretion independently of its effect on PKC activity. Moreover, conditions that increase PKC activity did not increase apo B secretion. Cell-permeable analogs of ceramide decreased immunoreactive apo B secretion. Sphingosine was without effect. The hydrolysis of membrane sphingomyelin by intestinal or pancreatic neutral sphingomyelinase may lead to the accumulation of cellular ceramide, which, in turn, could inhibit triacylglycerol-rich lipoprotein secretion.

Cholesterol Esters - metabolism

Apolipoproteins B - metabolism

Ceramides - metabolism

Sphingomyelins - metabolism

Tetradecanoylphorbol Acetate - pharmacology

Cell Survival

Methionine - metabolism

Humans

Type C Phospholipases - metabolism

Sulfur Radioisotopes

Apolipoproteins B - biosynthesis

Intestines - metabolism

Lipids - biosynthesis

RNA, Messenger - metabolism

Ceramides - pharmacology

Triglycerides - metabolism

Hydrolysis

Protein Kinase C - metabolism

Sphingomyelin Phosphodiesterase - metabolism

Cell Membrane - metabolism

Kinetics

Phospholipids - metabolism

Tumor Cells, Cultured

Colonic Neoplasms

Details

Title: Subtitle: Release of ceramide after membrane sphingomyelin hydrolysis decreases the basolateral secretion of triacylglycerol and apolipoprotein B in cultured human intestinal cells
Creators: F Jeffrey Field - Department of Internal Medicine, University of Iowa, Iowa City
Heshun Chen
Ella Born
Brad Dixon
Satya Mathur
Resource Type: Journal article
Publication Details: The Journal of clinical investigation, Vol.92(6), pp.2609-2619
DOI: 10.1172/JCI116876
PMID: 8254018
PMCID: PMC288457
ISSN: 0021-9738
eISSN: 1558-8238
Grant note: HL 49264 / NHLBI NIH HHS HL 42377 / NHLBI NIH HHS
Language: English
Date published: 12/1993
Academic Unit: Gastroenterology and Hepatology; Nephrology; Internal Medicine
Record Identifier: 9984094512502771

Metrics

11 Record Views

29 Times Cited - Web of Science