期刊
JOURNAL OF PROTEOME RESEARCH
卷 21, 期 1, 页码 49-66出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.1c00447
关键词
human intestinal ischemia − reperfusion; proteomics; phosphoproteomics; mass spectrometry imaging; spatiotemporal data
资金
- NUTRIM, Maastricht University (NUTRIM Graduate Program)
- NWO [184.034.019, 015.010.046]
- Netherlands X-omics Initiative
- Ministry of Science and Technology of Costa Rica (MICITT)
- University of Costa Rica (UCR)
This study investigated the proteome and phosphoproteome changes in the human intestine during ischemia-reperfusion using LC-MS/MS and MSI techniques. The findings revealed alterations in proteins related to intestinal absorption, innate immunity, and extracellular matrix organization, as well as the activity of MAPK and CDK families during IR. The study highlights the importance of complementary use of different MS methodologies in understanding molecular changes during IR.
Intestinal ischemia-reperfusion (IR) injury is a severe clinical condition, and unraveling its pathophysiology is crucial to improve therapeutic strategies and reduce the high morbidity and mortality rates. Here, we studied the dynamic proteome and phosphoproteome in the human intestine during ischemia and reperfusion, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to gain quantitative information of thousands of proteins and phosphorylation sites, as well as mass spectrometry imaging (MSI) to obtain spatial information. We identified a significant decrease in abundance of proteins related to intestinal absorption, microvillus, and cell junction, whereas proteins involved in innate immunity, in particular the complement cascade, and extracellular matrix organization increased in abundance after IR. Differentially phosphorylated proteins were involved in RNA splicing events and cytoskeletal and cell junction organization. In addition, our analysis points to mitogen-activated protein kinase (MAPK) and cyclindependent kinase (CDK) families to be active kinases during IR. Finally, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) MSI presented peptide alterations in abundance and distribution, which resulted, in combination with Fouriertransform ion cyclotron resonance (FTICR) MSI and LC-MS/MS, in the annotation of proteins related to RNA splicing, the complement cascade, and extracellular matrix organization. This study expanded our understanding of the molecular changes that occur during IR in the human intestine and highlights the value of the complementary use of different MS-based methodologies.
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