Gcase and limp2 abnormalities in the liver of niemann pick type c mice
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10362/124966 |
Resumo: | Funding Information: This work was supported by the NWO-Building Blocks of Life: GlcCer grant to J.M.F.G.A: BBOL-2007247202. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. |
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oai:run.unl.pt:10362/124966 |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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Gcase and limp2 abnormalities in the liver of niemann pick type c miceGCaseGPNMBLIMP2LysosomeMacrophageNPCNPC1StorageCatalysisMolecular BiologySpectroscopyComputer Science ApplicationsPhysical and Theoretical ChemistryOrganic ChemistryInorganic ChemistryFunding Information: This work was supported by the NWO-Building Blocks of Life: GlcCer grant to J.M.F.G.A: BBOL-2007247202. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.The lysosomal storage disease Niemann–Pick type C (NPC) is caused by impaired cholesterol efflux from lysosomes, which is accompanied by secondary lysosomal accumulation of sph-ingomyelin and glucosylceramide (GlcCer). Similar to Gaucher disease (GD), patients deficient in glucocerebrosidase (GCase) degrading GlcCer, NPC patients show an elevated glucosylsphingosine and glucosylated cholesterol. In livers of mice lacking the lysosomal cholesterol efflux transporter NPC1, we investigated the expression of established biomarkers of lipid-laden macrophages of GD patients, their GCase status, and content on the cytosol facing glucosylceramidase GBA2 and lysoso-mal integral membrane protein type B (LIMP2), a transporter of newly formed GCase to lysosomes. Livers of 80-week-old Npc1−/− mice showed a partially reduced GCase protein and enzymatic activity. In contrast, GBA2 levels tended to be reciprocally increased with the GCase deficiency. In Npc1−/− liver, increased expression of lysosomal enzymes (cathepsin D, acid ceramidase) was observed as well as increased markers of lipid-stressed macrophages (GPNMB and galectin-3). Im-munohistochemistry showed that the latter markers are expressed by lipid laden Kupffer cells. Earlier reported increase of LIMP2 in Npc1−/− liver was confirmed. Unexpectedly, immunohistochemistry showed that LIMP2 is particularly overexpressed in the hepatocytes of the Npc1−/− liver. LIMP2 in these hepatocytes seems not to only localize to (endo)lysosomes. The recent recognition that LIMP2 harbors a cholesterol channel prompts the speculation that LIMP2 in Npc1−/− hepatocytes might mediate export of cholesterol into the bile and thus protects the hepatocytes.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNvan der Lienden, Martijn J.C.Aten, JanMarques, André R.A.Waas, Ingeborg S.E.Larsen, Per W.B.Claessen, Nikevan der Wel, Nicole N.Ottenhoff, Roelofvan Eijk, MarcoAerts, Johannes M.F.G.2021-09-22T02:13:43Z2021-03-012021-03-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article15application/pdfhttp://hdl.handle.net/10362/124966eng1661-6596PURE: 33748479https://doi.org/10.3390/ijms22052532info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:06:10Zoai:run.unl.pt:10362/124966Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:45:37.086636Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Gcase and limp2 abnormalities in the liver of niemann pick type c mice |
| title |
Gcase and limp2 abnormalities in the liver of niemann pick type c mice |
| spellingShingle |
Gcase and limp2 abnormalities in the liver of niemann pick type c mice van der Lienden, Martijn J.C. GCase GPNMB LIMP2 Lysosome Macrophage NPC NPC1 Storage Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry |
| title_short |
Gcase and limp2 abnormalities in the liver of niemann pick type c mice |
| title_full |
Gcase and limp2 abnormalities in the liver of niemann pick type c mice |
| title_fullStr |
Gcase and limp2 abnormalities in the liver of niemann pick type c mice |
| title_full_unstemmed |
Gcase and limp2 abnormalities in the liver of niemann pick type c mice |
| title_sort |
Gcase and limp2 abnormalities in the liver of niemann pick type c mice |
| author |
van der Lienden, Martijn J.C. |
| author_facet |
van der Lienden, Martijn J.C. Aten, Jan Marques, André R.A. Waas, Ingeborg S.E. Larsen, Per W.B. Claessen, Nike van der Wel, Nicole N. Ottenhoff, Roelof van Eijk, Marco Aerts, Johannes M.F.G. |
| author_role |
author |
| author2 |
Aten, Jan Marques, André R.A. Waas, Ingeborg S.E. Larsen, Per W.B. Claessen, Nike van der Wel, Nicole N. Ottenhoff, Roelof van Eijk, Marco Aerts, Johannes M.F.G. |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Centro de Estudos de Doenças Crónicas (CEDOC) RUN |
| dc.contributor.author.fl_str_mv |
van der Lienden, Martijn J.C. Aten, Jan Marques, André R.A. Waas, Ingeborg S.E. Larsen, Per W.B. Claessen, Nike van der Wel, Nicole N. Ottenhoff, Roelof van Eijk, Marco Aerts, Johannes M.F.G. |
| dc.subject.por.fl_str_mv |
GCase GPNMB LIMP2 Lysosome Macrophage NPC NPC1 Storage Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry |
| topic |
GCase GPNMB LIMP2 Lysosome Macrophage NPC NPC1 Storage Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry |
| description |
Funding Information: This work was supported by the NWO-Building Blocks of Life: GlcCer grant to J.M.F.G.A: BBOL-2007247202. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021-09-22T02:13:43Z 2021-03-01 2021-03-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/124966 |
| url |
http://hdl.handle.net/10362/124966 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
1661-6596 PURE: 33748479 https://doi.org/10.3390/ijms22052532 |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
| dc.format.none.fl_str_mv |
15 application/pdf |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799138060463505408 |