Characterization of acid sphingomyelinase activity in human cerebrospinal fluid.

<h4>Background</h4>As a key enzyme in sphingolipid metabolism, acid sphingomyelinase (ASM) is involved in the regulation of cell fate and signaling via hydrolysis of sphingomyelin to form ceramide. While increased activity of the lysosomal form has been associated with various pathologic...

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Autores principales:	Christiane Mühle, Hagen B Huttner, Silke Walter, Martin Reichel, Fabio Canneva, Piotr Lewczuk, Erich Gulbins, Johannes Kornhuber
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/86f8450dfff845e0a0c455892811ea34
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spelling	oai:doaj.org-article:86f8450dfff845e0a0c455892811ea342021-11-18T07:47:01ZCharacterization of acid sphingomyelinase activity in human cerebrospinal fluid.1932-620310.1371/journal.pone.0062912https://doaj.org/article/86f8450dfff845e0a0c455892811ea342013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23658784/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>As a key enzyme in sphingolipid metabolism, acid sphingomyelinase (ASM) is involved in the regulation of cell fate and signaling via hydrolysis of sphingomyelin to form ceramide. While increased activity of the lysosomal form has been associated with various pathological conditions, there are few studies on secretory ASM limited only to cell models, plasma or serum.<h4>Methods</h4>An optimized assay based on a fluorescent substrate was applied to measure the ASM activity in cerebrospinal fluid (CSF) collected from mice and from 42 patients who were classified as controls based on normal routine CSF values.<h4>Results</h4>We have detected ASM activity in human CSF, established a sensitive quantitative assay and characterized the enzyme's properties. The enzyme resembles plasmatic ASM including protein stability and Zn(2+)-dependence but the assays differ considerably in the optimal detergent concentration. Significantly increased activities in the CSF of ASM transgenic mice and undetectable levels in ASM knock-out mice prove that the measured ASM activity originates from the ASM-encoding gene SMPD1. CSF localized ASM activities were comparable to corresponding serum ASM levels at their respective optimal reaction conditions, but no correlation was observed. The large variance in ASM activity was independent of sex, age or analyzed routine CSF parameters.<h4>Conclusions</h4>Human and mouse CSF contain detectable levels of secretory ASM, which are unrelated to serum ASM activities. Further investigations in humans and in animal models will help to elucidate the role of this enzyme in human disease and to assess its value as a potential biomarker for disease type, severity, progress or therapeutic success.Christiane MühleHagen B HuttnerSilke WalterMartin ReichelFabio CannevaPiotr LewczukErich GulbinsJohannes KornhuberPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e62912 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christiane Mühle Hagen B Huttner Silke Walter Martin Reichel Fabio Canneva Piotr Lewczuk Erich Gulbins Johannes Kornhuber Characterization of acid sphingomyelinase activity in human cerebrospinal fluid.
description	<h4>Background</h4>As a key enzyme in sphingolipid metabolism, acid sphingomyelinase (ASM) is involved in the regulation of cell fate and signaling via hydrolysis of sphingomyelin to form ceramide. While increased activity of the lysosomal form has been associated with various pathological conditions, there are few studies on secretory ASM limited only to cell models, plasma or serum.<h4>Methods</h4>An optimized assay based on a fluorescent substrate was applied to measure the ASM activity in cerebrospinal fluid (CSF) collected from mice and from 42 patients who were classified as controls based on normal routine CSF values.<h4>Results</h4>We have detected ASM activity in human CSF, established a sensitive quantitative assay and characterized the enzyme's properties. The enzyme resembles plasmatic ASM including protein stability and Zn(2+)-dependence but the assays differ considerably in the optimal detergent concentration. Significantly increased activities in the CSF of ASM transgenic mice and undetectable levels in ASM knock-out mice prove that the measured ASM activity originates from the ASM-encoding gene SMPD1. CSF localized ASM activities were comparable to corresponding serum ASM levels at their respective optimal reaction conditions, but no correlation was observed. The large variance in ASM activity was independent of sex, age or analyzed routine CSF parameters.<h4>Conclusions</h4>Human and mouse CSF contain detectable levels of secretory ASM, which are unrelated to serum ASM activities. Further investigations in humans and in animal models will help to elucidate the role of this enzyme in human disease and to assess its value as a potential biomarker for disease type, severity, progress or therapeutic success.
format	article
author	Christiane Mühle Hagen B Huttner Silke Walter Martin Reichel Fabio Canneva Piotr Lewczuk Erich Gulbins Johannes Kornhuber
author_facet	Christiane Mühle Hagen B Huttner Silke Walter Martin Reichel Fabio Canneva Piotr Lewczuk Erich Gulbins Johannes Kornhuber
author_sort	Christiane Mühle
title	Characterization of acid sphingomyelinase activity in human cerebrospinal fluid.
title_short	Characterization of acid sphingomyelinase activity in human cerebrospinal fluid.
title_full	Characterization of acid sphingomyelinase activity in human cerebrospinal fluid.
title_fullStr	Characterization of acid sphingomyelinase activity in human cerebrospinal fluid.
title_full_unstemmed	Characterization of acid sphingomyelinase activity in human cerebrospinal fluid.
title_sort	characterization of acid sphingomyelinase activity in human cerebrospinal fluid.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/86f8450dfff845e0a0c455892811ea34
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Characterization of acid sphingomyelinase activity in human cerebrospinal fluid.

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