Journal
BIOANALYSIS
Volume 11, Issue 11, Pages 1067-1083Publisher
FUTURE SCI LTD
DOI: 10.4155/bio-2018-0232
Keywords
AJS-ESI; biomarker; ion funnel; mass spectrometry; Niemann-Pick type C1; NPC; proteomics; thermal gradient focusing
Funding
- National Institutes of Health [R01 NS053677]
- UIC DFI Fellowship Program
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Aim: 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. Materials & methods: 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. Results: Using the standard-flow ESI approach, we found altered protein levels including, increased Limp2 and Rab7a in liver tissue ofNpc1(-/-) compared to control mice. Conclusion: 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. [GRAPHICS] .
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