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Regional distribution of human trypsinogen 4 in human brain at mRNA and protein level
Júlia Tóth1, Erika Siklódi, Péter Medveczky
1Department of Biochemistry, Eötvös Loránd University, Pázmány Street 1/C, 1117 Budapest, Hungary.
Abstract:
Gene PRSS3 on chromosome 9 of the human genome encodes, due to alternative splicing, both mesotrypsinogen and trypsinogen 4. Mesotrypsinogen has long been known as a minor component of trypsinogens expressed in human pancreas, while the mRNA for trypsinogen 4 has recently been identified in brain and other human tissues. We measured the amount of trypsinogen 4 mRNA and the quantity of the protein as well in 17 selected areas of the human brain. Our data suggest that human trypsinogen 4 is widely but unevenly distributed in the human brain. By immunohistochemistry, here we show that this protease is localized in neurons and glial cells, predominantly in astrocytes. In addition to cellular immunoreactivity, human trypsinogen 4 immunopositive dots were detected in the extracellular matrix, supporting the view that human trypsinogen 4 might be released from the cells under special conditions.
Insights
Human trypsinogen 4, encoded by the PRSS3 gene, is found in various brain regions, localized in neurons and glial cells. This protease may also be released into the extracellular matrix.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- The PRSS3 gene encodes mesotrypsinogen and trypsinogen 4 via alternative splicing.
- Mesotrypsinogen is a known pancreatic trypsinogen, while trypsinogen 4 mRNA is newly identified in the brain and other tissues.
Purpose of the Study:
- To investigate the distribution and cellular localization of human trypsinogen 4 in the brain.
- To determine if human trypsinogen 4 is present in neurons and glial cells and potentially released extracellularly.
Main Methods:
- Quantitative analysis of trypsinogen 4 mRNA levels across 17 human brain regions.
- Immunohistochemistry to detect trypsinogen 4 protein localization in brain tissue.
- Assessment of cellular and extracellular presence of trypsinogen 4.
Main Results:
- Human trypsinogen 4 mRNA and protein are widely, yet unevenly, distributed throughout the human brain.
- Immunohistochemistry revealed trypsinogen 4 localization within neurons and glial cells, with a predominance in astrocytes.
- Extracellular immunopositive dots of trypsinogen 4 were observed, suggesting potential release from cells.
Conclusions:
- Human trypsinogen 4 is a brain-expressed protease with a distinct distribution pattern.
- The protease is found in both neuronal and glial cells, particularly astrocytes.
- Evidence suggests human trypsinogen 4 may be secreted, potentially playing roles in extracellular processes.
