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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23658784/?tool=EBI |
| _version_ | 1818459536505176064 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T23:15:55Z |
| format | Article |
| id | doaj.art-86f8450dfff845e0a0c455892811ea34 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T23:15:55Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-86f8450dfff845e0a0c455892811ea342022-12-21T22:44:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6291210.1371/journal.pone.0062912Characterization of acid sphingomyelinase activity in human cerebrospinal fluid.Christiane MühleHagen B HuttnerSilke WalterMartin ReichelFabio CannevaPiotr LewczukErich GulbinsJohannes Kornhuber<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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23658784/?tool=EBI |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | Characterization of acid sphingomyelinase activity in human cerebrospinal fluid. |
| title_sort | characterization of acid sphingomyelinase activity in human cerebrospinal fluid |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23658784/?tool=EBI |
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