Napredna pretraga

Pregled bibliografske jedinice broj: 965491

N-glycome of the lysosomal glycocalyx is altered in Niemann-Pick Type C disease model cells


Košiček, Marko; Gudelj, Ivan; Horvatić, Anita; Jović, Tanja; Vučković, Frano; Lauc, Gordan; Hećimović, Silva
N-glycome of the lysosomal glycocalyx is altered in Niemann-Pick Type C disease model cells // Molecular & cellular proteomics, 17 (2018), 4; 631-642 doi:10.1074/mcp.RA117.000129 (međunarodna recenzija, članak, znanstveni)


Naslov
N-glycome of the lysosomal glycocalyx is altered in Niemann-Pick Type C disease model cells

Autori
Košiček, Marko ; Gudelj, Ivan ; Horvatić, Anita ; Jović, Tanja ; Vučković, Frano ; Lauc, Gordan ; Hećimović, Silva

Izvornik
Molecular & cellular proteomics (1535-9476) 17 (2018), 4; 631-642

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Niemann-Pick Type C disease ; lysosomal dysfunction ; lysosomal glycocalyx ; neurodegeneration ; glycomics ; proteomics

Sažetak
Increasing evidence implicates lysosomal dysfunction in the pathogenesis of neurodegenerative diseases, including the rare inherited lysosomal storage disorders (LSDs) and the most common neurodegenerative diseases, such as Alzheimer's and Parkinson's disease (AD and PD). Although the triggers of the lysosomal impairment may involve the accumulated macromolecules or dysfunction of the lysosomal enzymes, the role of the lysosomal glycocalyx in the lysosomal (dys)function has not been studied. The goal of this work was to analyze whether there are changes in the lysosomal glycocalyx in a cellular model of a LSD Niemann-Pick type C disease (NPC). Using the ferrofluid nanoparticles we isolated lysosomal organelles from NPC1-null and CHOwt cells. The magnetically isolated lysosomal fractions were enriched with the lysosomal marker protein LAMP1 and showed the key features of NPC disease: 3-fold higher cholesterol content and 4–5 fold enlarged size of the particles compared with the lysosomal fractions of wt cells. These lysosomal fractions were further processed to isolate lysosomal membrane proteins using Triton X-114 and their N- glycome was analyzed by HILIC-UPLC. N-glycans presented in each chromatographic peak were elucidated using MALDI-TOF/TOF-MS. We detected changes in the N-glycosylation pattern of the lysosomal glycocalyx of NPC1-null versus wt cells which involved high-mannose and sialylated N-glycans. To the best of our knowledge this study is the first to report N- glycome profiling of the lysosomal glycocalyx in NPC disease cellular model and the first to report the specific changes in the lysosomal glycocalyx in NPC1-null cells. We speculate that changes in the lysosomal glycocalyx may contribute to lysosomal (dys)function. Further glycome profiling of the lysosomal glycocalyx in other LSDs as well as the most common neurodegenerative diseases, such as AD and PD, is necessary to better understand the role of the lysosomal glycocalyx and to reveal its potential contribution in lysosomal dysfunction leading to neurodegeneration.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Interdisciplinarne prirodne znanosti, Temeljne medicinske znanosti, Kognitivna znanost (prirodne, tehničke, biomedicina i zdravstvo, društvene i humanističke znanosti)



POVEZANOST RADA


Ustanove
Farmaceutsko-biokemijski fakultet, Zagreb,
Veterinarski fakultet, Zagreb,
Institut "Ruđer Bošković", Zagreb,
GENOS d.o.o.

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


Citati