Purification, localization, and expression of human intestinal alkaline sphingomyelinase Published, JLR Papers in Press, April 1, 2003. DOI 10.1194/jlr.M300037-JLR200

Sphingomyelin (SM) metabolism in the gut may have an impact on colon cancer development. In this study, we purified alkaline sphingomyelinase (alk-SMase) from human intestinal content, and studied its location in the mucosa, expression in colon cancer, and function on colon cancer cells. The enzyme was purified by a series of chromatographies. The molecular mass of the enzyme is 60 kDa, optimal pH is 8.5, and isoelectric point is 6.6. Under optimal conditions, 1 mg of the enzyme hydrolyzed 11 mM SM per hour. The properties of the enzyme are similar to those of rat intestinal alk-SMase but not to those of bacterial neutral SMase. Immunogold electronmicroscopy identified the enzyme on the microvillar membrane in endosome-like structures and in the Golgi complexes of human enterocytes. The expression and the activity of the enzyme were decreased in parallel in human colon cancer tissues compared with the adjacent normal tissue. The enzyme inhibited DNA biosynthesis and cell proliferation dose dependently and caused a reduction of SM in HT29 cells. Intestinal alk-SMase is localized in the enterocytes, down-regulated in human colon cancer, and may have antiproliferative effects on colon cancer cells.

• Publication year

  2003

• Venue

  Journal of Lipid Research

• Publication date

  2003-06-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1194/JLR.M300037-JLR200PMID 12671034
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Effects of Ursodeoxycholate and Other Bile Salts on Levels of Rat Intestinal Alkaline Sphingomyelinase (A Potential Implication in Tumorigenesis)

  2004cited by this paper
• Chronic Colitis Is Associated With a Reduction of Mucosal Alkaline Sphingomyelinase Activity

  2002cited by this paper
• Divergent role of ceramide generated by exogenous sphingomyelinases on NF‐κB activation and apoptosis in human colon HT‐29 cells

  2002cited by this paper
• Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells.

  2002cited by this paper
• Sphingoid Bases and Ceramide Induce Apoptosis in HT-29 and HCT-116 Human Colon Cancer Cells

  2002cited by this paper
• Effects of red meat and fiber in high fat diet on activities of sphingomyelinase, ceramidase and caspase-3 in rat colonic mucosa.

  2002cited by this paper
• Dietary sphingomyelin suppresses intestinal cholesterol absorption by decreasing thermodynamic activity of cholesterol monomers.

  2002cited by this paper
• Purification, characterization, and expression of rat intestinal alkaline sphingomyelinase.

  2002cited by this paper
• In search of vulcan: Where are all the iron men (and women)?

  2002cited by this paper
• Bile salt-stimulated carboxyl ester lipase influences lipoprotein assembly and secretion in intestine: a process mediated via ceramide hydrolysis.

  2001cited by this paper
• Lipid Rafts Exist as Stable Cholesterol-independent Microdomains in the Brush Border Membrane of Enterocytes*

  2001cited by this paper
• Modulation of intracellular beta-catenin localization and intestinal tumorigenesis in vivo and in vitro by sphingolipids.

  2001cited by this paper
• Sphingolipid hydrolyzing enzymes in the gastrointestinal tract.

  2000cited by this paper
• A mutual inhibitory effect on absorption of sphingomyelin and cholesterol.

  2000cited by this paper
• Molecular Cloning, Characterization, and Expression of a Novel Human Neutral Sphingomyelinase*

  1999cited by this paper
• Familial adenomatous polyposis is associated with a marked decrease in alkaline sphingomyelinase activity: a key factor to the unrestrained cell proliferation?

  1999cited by this paper
• Ursodeoxycholic acid increases the activities of alkaline sphingomyelinase and caspase-3 in the rat colon.

  1999cited by this paper
• Transport of cholesterol from the endoplasmic reticulum to the plasma membrane is constitutive in CaCo-2 cells and differs from the transport of plasma membrane cholesterol to the endoplasmic reticulum.

  1998cited by this paper
• Sphingomyelin hydrolysis in the gut and clinical implications in colorectal tumorigenesis and other gastrointestinal diseases.

  1998cited by this paper
• Regulation of ceramide production and apoptosis.

  1998cited by this paper
• Alkaline sphingomyelinase activity is decreased in human colorectal carcinoma

  1997cited by this paper
• Purification of a newly identified alkaline sphingomyelinase in human bile and effects of bile salts and phosphatidylcholine on enzyme activity

  1997cited by this paper
• Localization and capacity of sphingomyelin digestion in the rat intestinal tract

  1997cited by this paper
• Suppression of aberrant colonic crypt foci by synthetic sphingomyelins with saturated or unsaturated sphingoid base backbones.

  1997cited by this paper
• Importance of sphingolipids and inhibitors of sphingolipid metabolism as components of animal diets.

  1997cited by this paper
• Role of the ceramide-signaling pathway in cytokine responses to P- fimbriated Escherichia coli

  1996cited by this paper
• Sphingomyelin consumption suppresses aberrant colonic crypt foci and increases the proportion of adenomas versus adenocarcinomas in CF1 mice treated with 1,2-dimethylhydrazine: implications for dietary sphingolipids and colon carcinogenesis.

  1996cited by this paper
• Identification of an alkaline sphingomyelinase activity in human bile.

  1996cited by this paper
• Distribution of alkaline sphingomyelinase activity in human beings and animals

  1996cited by this paper
• Alkaline sphingomyelinase activity in rat gastrointestinal tract: distribution and characteristics.

  1995cited by this paper
• Distribution of three microvillar enzymes along the small intestinal crypt-villus axis.

  1994cited by this paper
• Dietary sphingomyelin inhibits 1,2-dimethylhydrazine-induced colon cancer in CF1 mice.

  1994cited by this paper
• Chemoprevention of azoxymethane-induced colonic carcinogenesis by supplemental dietary ursodeoxycholic acid.

  1994cited by this paper
• Sphingolipid breakdown products: anti-proliferative and tumor-suppressor lipids.

  1993cited by this paper
• Release of ceramide after membrane sphingomyelin hydrolysis decreases the basolateral secretion of triacylglycerol and apolipoprotein B in cultured human intestinal cells.

  1993cited by this paper
• Neutral sphingomyelinase.

  1993cited by this paper
• Sphingomyelin content of intestinal cell membranes regulates cholesterol absorption. Evidence for pancreatic and intestinal cell sphingomyelinase activity.

  1992cited by this paper
• Organelles involved in the intracellular transport of newly synthesized aminopeptidase N and their acidity.

  1989cited by this paper
• Isolation of cDNA clones encoding human acid sphingomyelinase: occurrence of alternatively processed transcripts.

  1989cited by this paper
• Premalignant alterations in the lipid composition and fluidity of colonic brush border membranes of rats administered 1,2 dimethylhydrazine.

  1986cited by this paper
• Chemical synthesis of choline-labeled lecithins and sphingomyelins.

  1975cited by this paper
• The presence of spingomyelin- and ceramide-cleaving enzymes in the small intestinal tract.

  1969cited by this paper
• A rapid method of total lipid extraction and purification.

  1959influential reference

• Non-Pancreatic Digestive Enzymes

  2025cites this paper
• Production and purification of tag-free recombinant human acid sphingomyelinase in Nicotiana benthamiana

  2025cites this paper
• Ceramides are Fuel Gauges on the Drive to Cardiometabolic Disease.

  2024cites this paper
• System Analysis Based on Lipid-Metabolism-Related Genes Identifies AGT as a Novel Therapy Target for Gastric Cancer with Neoadjuvant Chemotherapy

  2023cites this paper
• Identification of biomarkers for glycaemic deterioration in type 2 diabetes

  2023cites this paper
• Transcriptome analysis alk-SMase knockout mice reveals the effect of alkaline sphingomyelinase on liver

  2022cites this paper
• The Role of Sphingomyelin and Ceramide in Motor Neuron Diseases

  2022cites this paper
• Transcriptome analysis of intestine from alk-SMase knockout mice reveals the effect of alk-SMase

  2022cites this paper
• Ceramide signaling in the gut.

  2022cites this paper
• Ceramide Transfer Protein (CERT): An Overlooked Molecular Player in Cancer

  2021cites this paper
• Cholesterol-phospholipid interactions resist the detergent effect of bovine bile.

  2021cites this paper
• Sphingolipid lysosomal storage diseases: from bench to bedside

  2021cites this paper
• Sphingomyelinases and Liver Diseases

  2020cites this paper
• Pancreatic and mucosal enzymes in choline phospholipid digestion.

  2019cites this paper
• New factors for protein transport identified by a genome-wide CRISPRi screen in mammalian cells

  2019cites this paper
• Sphingolipids and Redox Signaling in Renal Regulation and Chronic Kidney Diseases

  2018cites this paper
• Alkaline sphingomyelinase (NPP7) in hepatobiliary diseases: A field that needs to be closely studied

  2018cites this paper
• Dietary and Endogenous Sphingolipid Metabolism in Chronic Inflammation

  2017cites this paper
• Crystal structure of the human alkaline sphingomyelinase provides insights into substrate recognition

  2017influential citation
• An LC/MS/MS method for quantitation of chemopreventive sphingadienes in food products and biological samples.

  2017cites this paper
• Targeting Phospholipid Metabolism in Cancer

  2016cites this paper
• Fecal metabolome of the Hadza hunter-gatherers: a host-microbiome integrative view

  2016cites this paper
• Sphingolipids as Mediators in the Crosstalk between Microbiota and Intestinal Cells: Implications for Inflammatory Bowel Disease

  2016cites this paper
• Trafficking and Functions of Bioactive Sphingolipids: Lessons from Cells and Model Membranes

  2015cites this paper
• Trafficking and Functions of Bioactive Sphingolipids: Lessons from Cells and Model Membranes Supplementary Issue: Cellular Anatomy of Lipid Traffic

  2015cites this paper
• Regulation and function of acid sphingomyelinase (ASM)/ceramide pathway in irradiation-induced cell death

  2015cites this paper
• Enhanced Colonic Tumorigenesis in Alkaline Sphingomyelinase (NPP7) Knockout Mice

  2014cites this paper
• Metabolism, Physiological Role, and Clinical Implications of Sphingolipids in Gastrointestinal Tract

  2013cites this paper
• Assessment of nutritional status and analytical methods.

  2012cites this paper
• Rola sfingolipidów w układzie pokarmowym Role of sphingolipids in digestive system

  2012cites this paper
• Atlas of Genetics and Cytogenetics in Oncology and Haematology

  2012cites this paper
• [Role of sphingolipids in digestive system].

  2012cites this paper
• Chapter 8 – Sphingolipids

  2012cites this paper
• Molecular modeling of human alkaline sphingomyelinase

  2011cites this paper
• The effect of milk polar lipids separated from butter serum on the lipid levels in the liver and the plasma of obese-model mouse (KK-Ay)

  2011cites this paper
• ENPP7 (ectonucleotide pyrophosphatase/phosphodiesterase 7)

  2011cites this paper
• Dysregulation of sphingolipid metabolism in cancer

  2011cites this paper
• Crucial role of alkaline sphingomyelinase in sphingomyelin digestion: a study on enzyme knockout mice

  2011cites this paper
• Composition, Properties and Nutritional Aspects of Milk Fat Globule Membrane - a Review

  2011cites this paper
• An overview of sphingolipid metabolism: from synthesis to breakdown.

  2010cites this paper
• Generating Ceramide from Sphingomyelin by Alkaline Sphingomyelinase in the Gut Enhances Sphingomyelin-Induced Inhibition of Cholesterol Uptake in Caco-2 Cells

  2010cites this paper
• Characterization of non-lipid autotaxin inhibitors.

  2010cites this paper
• Optimization of a pipemidic acid autotaxin inhibitor.

  2010cites this paper
• Metabolism of sphingolipids in the gut and its relation to inflammation and cancer development.

  2009cites this paper
• Matrix metalloproteinase‐1 expression induced by IL‐1β requires acid sphingomyelinase

  2009cites this paper
• Expression of Alkaline Sphingomyelinase in Yeast Cells and Anti-inflammatory Effects of the Expressed Enzyme in a Rat Colitis Model

  2009influential citation
• Plant Sphingolipids: Structure, Synthesis and Function

  2009cites this paper
• Ceramide activates JNK to inhibit a cAMP‐gated K+ conductance and Cl‐ secretion in intestinal epithelia

  2009cites this paper
• The potential of sphingomyelin as a chemopreventive agent in AOM-induced colon cancer model: wild-type and p53+/- mice.

  2008cites this paper
• Propofol Pretreatment Reduces Ceramide Production and Attenuates Intestinal Mucosal Apoptosis Induced by Intestinal Ischemia/Reperfusion in Rats

  2008cites this paper
• Nutritional and technological aspects of milk fat globule membrane material

  2008cites this paper
• Identification of Mg2+-dependent Neutral Sphingomyelinase 1 as a Mediator of Heat Stress-induced Ceramide Generation and Apoptosis*

  2008cites this paper
• Dietary sphingomyelin inhibits colonic tumorigenesis with an up-regulation of alkaline sphingomyelinase expression in ICR mice.

  2008cites this paper
• VSL#3 probiotic upregulates intestinal mucosal alkaline sphingomyelinase and reduces inflammation.

  2008cites this paper
• Sphingolipids in the gut? Which are the important issues?

  2007cites this paper
• The metabolism and function of sphingolipids and glycosphingolipids

  2007cites this paper
• Conversion of apical plasma membrane sphingomyelin to ceramide attenuates the intoxication of host cells by cholera toxin

  2007influential citation
• Effects of bile diversion in rats on intestinal sphingomyelinases and ceramidase.

  2007cites this paper
• Sphingomyelinase and ceramidase in the intestinal tract

  2007cites this paper
• Human Meconium Contains Significant Amounts of Alkaline Sphingomyelinase, Neutral Ceramidase, and Sphingolipid Metabolites

  2007cites this paper
• Ursolic acid and other pentacyclic triterpenoids stimulate intestinal alkaline sphingomyelinase in vitro

  2006cites this paper
• Absorption and lipoprotein transport of sphingomyelin Published, JLR Papers in Press, October 26, 2005.

  2006cites this paper
• Alkaline sphingomyelinase: an old enzyme with novel implications.

  2006cites this paper
• Sphingolipids as targets for microbial infections.

  2006cites this paper
• Ursodeoxycholic acid differentially affects three types of sphingomyelinase in human colon cancer Caco 2 cells.

  2006cites this paper
• Intestinal alkaline sphingomyelinase hydrolyses and inactivates platelet-activating factor by a phospholipase C activity.

  2006cites this paper
• Composition, Structure and Absorption of Milk Lipids: A Source of Energy, Fat-Soluble Nutrients and Bioactive Molecules

  2006cites this paper
• Functional studies of human intestinal alkaline sphingomyelinase by deglycosylation and mutagenesis.

  2005cites this paper
• Cloning of alkaline sphingomyelinase from rat intestinal mucosa and adjusting of the hypothetical protein XP_221184 in GenBank.

  2005cites this paper
• Detection of Alkaline Sphingomyelinase Activity in Human Stool: Proposed Role as a New Diagnostic and Prognostic Marker of Colorectal Cancer

  2005cites this paper
• Pancreatic trypsin cleaves intestinal alkaline sphingomyelinase from mucosa and enhances the sphingomyelinase activity.

  2004cites this paper
• Psyllium and fat in diets differentially affect the activities and expressions of colonic sphingomyelinases and caspase in mice.

  2004influential citation
• 18 – Anti-angiogenic functional food, degenerative disease and cancer

  2004cites this paper
• Rat intestinal ceramidase: purification, properties, and physiological relevance.

  2004cites this paper
• Identification of one exon deletion of intestinal alkaline sphingomyelinase in colon cancer HT-29 cells and a differentiation-related expression of the wild-type enzyme in Caco-2 cells.

  2004cites this paper
• Identification of Human Intestinal Alkaline Sphingomyelinase as a Novel Ecto-enzyme Related to the Nucleotide Phosphodiesterase Family*

  2003cites this paper