Melissa R Pergande1, Estefania Zarate1, Carol Haney-Ball2, Cristin D Davidson3, Giuseppe Scesa4, Maria I Givogri4, Ernesto R Bongarzone4, Stephanie M Cologna1,5. 1. Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA. 2. Agilent Technologies, Cary, NC 27518, USA. 3. Albert Einstein College of Medicine, Bronx, NY 10461, USA. 4. Department of Anatomy & Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA. 5. Laboratory for Integrative Neuroscience, University of Illinois at Chicago, Chicago, IL 60607, USA.
Abstract
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 of Npc1-/- 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.
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 NPC1mouse 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 of Npc1-/- 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.
Entities:
Keywords:
AJS-ESI; NPC; Niemann–Pick type C1; biomarker; ion funnel; mass spectrometry; proteomics; thermal gradient focusing
Authors: Koralege C Pathmasiri; Melissa R Pergande; Fernando Tobias; Rima Rebiai; Avia Rosenhouse-Dantsker; Ernesto R Bongarzone; Stephanie M Cologna Journal: J Lipid Res Date: 2020-05-05 Impact factor: 5.922
Authors: Antony Cougnoux; Julia C Yerger; Mason Fellmeth; Jenny Serra-Vinardell; Kyle Martin; Fatemeh Navid; James Iben; Christopher A Wassif; Niamh X Cawley; Forbes D Porter Journal: Int J Mol Sci Date: 2020-07-28 Impact factor: 5.923
Authors: Martijn J C van der Lienden; Jan Aten; André R A Marques; Ingeborg S E Waas; Per W B Larsen; Nike Claessen; Nicole N van der Wel; Roelof Ottenhoff; Marco van Eijk; Johannes M F G Aerts Journal: Int J Mol Sci Date: 2021-03-03 Impact factor: 5.923