Fabry disease: renal sphingolipid distribution in the α-Gal A knockout mouse model by mass spectrometric and immunohistochemical imaging
Fabry disease is an X-linked lysosomal storage disease due to deficient α-galactosidase A (α-Gal A) activity and the resultant lysosomal accumulation of globotriaosylceramide (Gb3) and related lipids primarily in blood vessels, kidney, heart, and other organs. The renal distribution of stored glycol...
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| Veröffentlicht in: | Analytical and bioanalytical chemistry 2015-03, Vol.407 (8), p.2283-2291 |
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| creator | Kuchar, Ladislav Faltyskova, Helena Krasny, Lukas Dobrovolny, Robert Hulkova, Helena Ledvinova, Jana Volny, Michael Strohalm, Martin Lemr, Karel Kryspinova, Lenka Asfaw, Befekadu Rybová, Jitka Desnick, Robert J. Havlicek, Vladimir |
| description | Fabry disease is an X-linked lysosomal storage disease due to deficient α-galactosidase A (α-Gal A) activity and the resultant lysosomal accumulation of globotriaosylceramide (Gb3) and related lipids primarily in blood vessels, kidney, heart, and other organs. The renal distribution of stored glycolipid species in the α-Gal A knockout mouse model was compared to that in mice to assess relative distribution and absolute amounts of accumulated sphingolipid isoforms. Twenty isoforms of five sphingolipid groups were visualized by mass spectrometry imaging (MSI), and their distribution was compared with immunohistochemical (IHC) staining of Gb3, the major stored glycosphingolipid in consecutive tissue sections. Quantitative bulk lipid analysis of tissue sections was assessed by electrospray ionization with tandem mass spectrometry (ESI-MS/MS). In contrast to the findings in wild-type mice, all three analytical techniques (MSI, IHC, and ESI-MS/MS) revealed increases in Gb3 isoforms and ceramide dihexosides (composed mostly of galabiosylceramides), respectively. To our knowledge, this is the first report of the distribution of individual molecular species of Gb3 and galabiosylceramides in kidney sections in Fabry disease mouse. In addition, the spatial distribution of ceramides, ceramide monohexosides, and sphingomyelin forms in renal tissue is presented and discussed in the context of their biosynthesis.
Graphical Abstract
Immunohistochemical images of a wild type (
left
) and Fabry mouse kidney (
right
) |
| doi_str_mv | 10.1007/s00216-014-8402-7 |
| format | Article |
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Graphical Abstract
Immunohistochemical images of a wild type (
left
) and Fabry mouse kidney (
right
)</description><identifier>ISSN: 1618-2642</identifier><identifier>EISSN: 1618-2650</identifier><identifier>DOI: 10.1007/s00216-014-8402-7</identifier><identifier>PMID: 25542581</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>alpha-Galactosidase - genetics ; alpha-Galactosidase - metabolism ; Analytical Chemistry ; Animals ; Biochemistry ; Blood vessels ; Characterization and Evaluation of Materials ; Chemistry ; Chemistry and Materials Science ; Disease Models, Animal ; Fabry Disease - enzymology ; Fabry Disease - genetics ; Fabry Disease - metabolism ; Food Science ; Humans ; Imaging ; Immunochemistry ; Kidney - chemistry ; Kidney - metabolism ; Kidneys ; Laboratory Medicine ; Lipids ; Mass Spectrometry ; Mass Spectrometry Imaging ; Mathematical analysis ; Mice ; Mice, Knockout ; Monitoring/Environmental Analysis ; Organs ; Research Paper ; Spatial distribution ; Sphingolipids - chemistry ; Sphingolipids - metabolism</subject><ispartof>Analytical and bioanalytical chemistry, 2015-03, Vol.407 (8), p.2283-2291</ispartof><rights>Springer-Verlag Berlin Heidelberg 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c550t-b38adfd9d6234f162f8648c91e4db66ea7e293c90d64c0794496867eac783e063</citedby><cites>FETCH-LOGICAL-c550t-b38adfd9d6234f162f8648c91e4db66ea7e293c90d64c0794496867eac783e063</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00216-014-8402-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00216-014-8402-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25542581$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kuchar, Ladislav</creatorcontrib><creatorcontrib>Faltyskova, Helena</creatorcontrib><creatorcontrib>Krasny, Lukas</creatorcontrib><creatorcontrib>Dobrovolny, Robert</creatorcontrib><creatorcontrib>Hulkova, Helena</creatorcontrib><creatorcontrib>Ledvinova, Jana</creatorcontrib><creatorcontrib>Volny, Michael</creatorcontrib><creatorcontrib>Strohalm, Martin</creatorcontrib><creatorcontrib>Lemr, Karel</creatorcontrib><creatorcontrib>Kryspinova, Lenka</creatorcontrib><creatorcontrib>Asfaw, Befekadu</creatorcontrib><creatorcontrib>Rybová, Jitka</creatorcontrib><creatorcontrib>Desnick, Robert J.</creatorcontrib><creatorcontrib>Havlicek, Vladimir</creatorcontrib><title>Fabry disease: renal sphingolipid distribution in the α-Gal A knockout mouse model by mass spectrometric and immunohistochemical imaging</title><title>Analytical and bioanalytical chemistry</title><addtitle>Anal Bioanal Chem</addtitle><addtitle>Anal Bioanal Chem</addtitle><description>Fabry disease is an X-linked lysosomal storage disease due to deficient α-galactosidase A (α-Gal A) activity and the resultant lysosomal accumulation of globotriaosylceramide (Gb3) and related lipids primarily in blood vessels, kidney, heart, and other organs. The renal distribution of stored glycolipid species in the α-Gal A knockout mouse model was compared to that in mice to assess relative distribution and absolute amounts of accumulated sphingolipid isoforms. Twenty isoforms of five sphingolipid groups were visualized by mass spectrometry imaging (MSI), and their distribution was compared with immunohistochemical (IHC) staining of Gb3, the major stored glycosphingolipid in consecutive tissue sections. Quantitative bulk lipid analysis of tissue sections was assessed by electrospray ionization with tandem mass spectrometry (ESI-MS/MS). In contrast to the findings in wild-type mice, all three analytical techniques (MSI, IHC, and ESI-MS/MS) revealed increases in Gb3 isoforms and ceramide dihexosides (composed mostly of galabiosylceramides), respectively. To our knowledge, this is the first report of the distribution of individual molecular species of Gb3 and galabiosylceramides in kidney sections in Fabry disease mouse. In addition, the spatial distribution of ceramides, ceramide monohexosides, and sphingomyelin forms in renal tissue is presented and discussed in the context of their biosynthesis.
Graphical Abstract
Immunohistochemical images of a wild type (
left
) and Fabry mouse kidney (
right
)</description><subject>alpha-Galactosidase - genetics</subject><subject>alpha-Galactosidase - metabolism</subject><subject>Analytical Chemistry</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Blood vessels</subject><subject>Characterization and Evaluation of Materials</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Disease Models, Animal</subject><subject>Fabry Disease - enzymology</subject><subject>Fabry Disease - genetics</subject><subject>Fabry Disease - metabolism</subject><subject>Food Science</subject><subject>Humans</subject><subject>Imaging</subject><subject>Immunochemistry</subject><subject>Kidney - chemistry</subject><subject>Kidney - metabolism</subject><subject>Kidneys</subject><subject>Laboratory Medicine</subject><subject>Lipids</subject><subject>Mass Spectrometry</subject><subject>Mass Spectrometry Imaging</subject><subject>Mathematical analysis</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Monitoring/Environmental Analysis</subject><subject>Organs</subject><subject>Research Paper</subject><subject>Spatial distribution</subject><subject>Sphingolipids - chemistry</subject><subject>Sphingolipids - metabolism</subject><issn>1618-2642</issn><issn>1618-2650</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcFOHSEUhknTplr1AboxLLuZCgzDgDtjqjYxcWPXhIEz96IDXGFmcR-hj9MX6TPJzbUurRs4yfnOfwIfQl8p-U4J6c8KIYyKhlDeSE5Y039Ah1RQ2TDRkY-vNWcH6EspD4TQTlLxGR2wruOs1ofo95UZ8hY7X8AUOMcZoplw2ax9XKXJb7zb9ebsh2X2KWIf8bwG_PdPc125C_wYk31My4xDWgrU08GEhy0OppQaA3bOKUCdt9hEh30IS0zrmpjsGoK3NcQHs6rbjtGn0UwFTl7uI_Tr6sf95U1ze3f98_LitrFdR-ZmaKVxo1NOsJaPVLBRCi6tosDdIASYHphqrSJOcEt6xbkSUvRgbC9bIKI9Qt_2uZucnhYosw6-WJgmE6G-QdOeC6mEUu3_USE7SSiV3TvQqoFSRmRF6R61OZWSYdSbXP8gbzUleudV773q6lXvvOq-zpy-xC9DAPc68U9kBdgeKLUVV5D1Q1pydVneSH0Gjvmvhg</recordid><startdate>20150301</startdate><enddate>20150301</enddate><creator>Kuchar, Ladislav</creator><creator>Faltyskova, Helena</creator><creator>Krasny, Lukas</creator><creator>Dobrovolny, Robert</creator><creator>Hulkova, Helena</creator><creator>Ledvinova, Jana</creator><creator>Volny, Michael</creator><creator>Strohalm, Martin</creator><creator>Lemr, Karel</creator><creator>Kryspinova, Lenka</creator><creator>Asfaw, Befekadu</creator><creator>Rybová, Jitka</creator><creator>Desnick, Robert J.</creator><creator>Havlicek, Vladimir</creator><general>Springer Berlin Heidelberg</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><scope>7QH</scope><scope>7UA</scope><scope>C1K</scope></search><sort><creationdate>20150301</creationdate><title>Fabry disease: renal sphingolipid distribution in the α-Gal A knockout mouse model by mass spectrometric and immunohistochemical imaging</title><author>Kuchar, Ladislav ; Faltyskova, Helena ; Krasny, Lukas ; Dobrovolny, Robert ; Hulkova, Helena ; Ledvinova, Jana ; Volny, Michael ; Strohalm, Martin ; Lemr, Karel ; Kryspinova, Lenka ; Asfaw, Befekadu ; Rybová, Jitka ; Desnick, Robert J. ; Havlicek, Vladimir</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c550t-b38adfd9d6234f162f8648c91e4db66ea7e293c90d64c0794496867eac783e063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>alpha-Galactosidase - genetics</topic><topic>alpha-Galactosidase - metabolism</topic><topic>Analytical Chemistry</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Blood vessels</topic><topic>Characterization and Evaluation of Materials</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Disease Models, Animal</topic><topic>Fabry Disease - enzymology</topic><topic>Fabry Disease - genetics</topic><topic>Fabry Disease - metabolism</topic><topic>Food Science</topic><topic>Humans</topic><topic>Imaging</topic><topic>Immunochemistry</topic><topic>Kidney - chemistry</topic><topic>Kidney - metabolism</topic><topic>Kidneys</topic><topic>Laboratory Medicine</topic><topic>Lipids</topic><topic>Mass Spectrometry</topic><topic>Mass Spectrometry Imaging</topic><topic>Mathematical analysis</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Monitoring/Environmental Analysis</topic><topic>Organs</topic><topic>Research Paper</topic><topic>Spatial distribution</topic><topic>Sphingolipids - chemistry</topic><topic>Sphingolipids - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kuchar, Ladislav</creatorcontrib><creatorcontrib>Faltyskova, Helena</creatorcontrib><creatorcontrib>Krasny, Lukas</creatorcontrib><creatorcontrib>Dobrovolny, Robert</creatorcontrib><creatorcontrib>Hulkova, Helena</creatorcontrib><creatorcontrib>Ledvinova, Jana</creatorcontrib><creatorcontrib>Volny, Michael</creatorcontrib><creatorcontrib>Strohalm, Martin</creatorcontrib><creatorcontrib>Lemr, Karel</creatorcontrib><creatorcontrib>Kryspinova, Lenka</creatorcontrib><creatorcontrib>Asfaw, Befekadu</creatorcontrib><creatorcontrib>Rybová, Jitka</creatorcontrib><creatorcontrib>Desnick, Robert J.</creatorcontrib><creatorcontrib>Havlicek, Vladimir</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Aqualine</collection><collection>Water Resources Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Analytical and bioanalytical chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kuchar, Ladislav</au><au>Faltyskova, Helena</au><au>Krasny, Lukas</au><au>Dobrovolny, Robert</au><au>Hulkova, Helena</au><au>Ledvinova, Jana</au><au>Volny, Michael</au><au>Strohalm, Martin</au><au>Lemr, Karel</au><au>Kryspinova, Lenka</au><au>Asfaw, Befekadu</au><au>Rybová, Jitka</au><au>Desnick, Robert J.</au><au>Havlicek, Vladimir</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fabry disease: renal sphingolipid distribution in the α-Gal A knockout mouse model by mass spectrometric and immunohistochemical imaging</atitle><jtitle>Analytical and bioanalytical chemistry</jtitle><stitle>Anal Bioanal Chem</stitle><addtitle>Anal Bioanal Chem</addtitle><date>2015-03-01</date><risdate>2015</risdate><volume>407</volume><issue>8</issue><spage>2283</spage><epage>2291</epage><pages>2283-2291</pages><issn>1618-2642</issn><eissn>1618-2650</eissn><abstract>Fabry disease is an X-linked lysosomal storage disease due to deficient α-galactosidase A (α-Gal A) activity and the resultant lysosomal accumulation of globotriaosylceramide (Gb3) and related lipids primarily in blood vessels, kidney, heart, and other organs. The renal distribution of stored glycolipid species in the α-Gal A knockout mouse model was compared to that in mice to assess relative distribution and absolute amounts of accumulated sphingolipid isoforms. Twenty isoforms of five sphingolipid groups were visualized by mass spectrometry imaging (MSI), and their distribution was compared with immunohistochemical (IHC) staining of Gb3, the major stored glycosphingolipid in consecutive tissue sections. Quantitative bulk lipid analysis of tissue sections was assessed by electrospray ionization with tandem mass spectrometry (ESI-MS/MS). In contrast to the findings in wild-type mice, all three analytical techniques (MSI, IHC, and ESI-MS/MS) revealed increases in Gb3 isoforms and ceramide dihexosides (composed mostly of galabiosylceramides), respectively. To our knowledge, this is the first report of the distribution of individual molecular species of Gb3 and galabiosylceramides in kidney sections in Fabry disease mouse. In addition, the spatial distribution of ceramides, ceramide monohexosides, and sphingomyelin forms in renal tissue is presented and discussed in the context of their biosynthesis.
Graphical Abstract
Immunohistochemical images of a wild type (
left
) and Fabry mouse kidney (
right
)</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>25542581</pmid><doi>10.1007/s00216-014-8402-7</doi><tpages>9</tpages></addata></record> |
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| subjects | alpha-Galactosidase - genetics alpha-Galactosidase - metabolism Analytical Chemistry Animals Biochemistry Blood vessels Characterization and Evaluation of Materials Chemistry Chemistry and Materials Science Disease Models, Animal Fabry Disease - enzymology Fabry Disease - genetics Fabry Disease - metabolism Food Science Humans Imaging Immunochemistry Kidney - chemistry Kidney - metabolism Kidneys Laboratory Medicine Lipids Mass Spectrometry Mass Spectrometry Imaging Mathematical analysis Mice Mice, Knockout Monitoring/Environmental Analysis Organs Research Paper Spatial distribution Sphingolipids - chemistry Sphingolipids - metabolism |
| title | Fabry disease: renal sphingolipid distribution in the α-Gal A knockout mouse model by mass spectrometric and immunohistochemical imaging |
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