Standard-flow LC and thermal focusing ESI elucidates altered liver proteins in late stage Niemann–Pick, type C1 disease

Mass spectrometry (MS)-based proteomics, particularly with the development of nano-ESI, have been invaluable to our understanding of altered proteins related to human disease. Niemann–Pick, type C1 (NPC1) disease is a fatal, autosomal recessive, neurodegenerative disorder. The resulting defects incl...

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Bibliographic Details
Published in:Bioanalysis 2019-06, Vol.11 (11), p.1067-1083
Main Authors: Pergande, Melissa R, Zarate, Estefania, Haney-Ball, Carol, Davidson, Cristin D, Scesa, Giuseppe, Givogri, Maria I, Bongarzone, Ernesto R, Cologna, Stephanie M
Format: Article
Language:English
Subjects:
AJS-ESI
biomarker
Biomarkers
Brain diseases
Cholesterol
Chromatography
Enzymes
Gas flow
Genetic disorders
Hereditary diseases
ion funnel
Liver diseases
mass spectrometry
Mass spectroscopy
Metabolic disorders
Neurodegenerative diseases
Niemann–Pick type C1
NPC
Npc1 protein
Peptides
Proteins
Proteomes
Proteomics
Sphingolipids
thermal gradient focusing
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Summary:Mass spectrometry (MS)-based proteomics, particularly with the development of nano-ESI, have been invaluable to our understanding of altered proteins related to human disease. Niemann–Pick, type C1 (NPC1) disease is a fatal, autosomal recessive, neurodegenerative disorder. The resulting defects include unesterified cholesterol and sphingolipids accumulation in the late endosomal/lysosomal system resulting in organ dysfunction including liver disease. First, we performed MS analysis of a complex mammalian proteome using both nano- and standard-flow ESI with the intent of developing a differential proteomics platform using standard-flow ESI. Next, we measured the differential liver proteome in the NPC1 mouse model via label-free quantitative MS using standard-flow ESI. Using the standard-flow ESI approach, we found altered protein levels including, increased Limp2 and Rab7a in liver tissue of  compared to control mice. Standard-flow ESI can be a tool for quantitative proteomic studies when sample amount is not limited. Using this method, we have identified new protein markers of NPC1.
ISSN:1757-6180
1757-6199
DOI:10.4155/bio-2018-0232