Involvement of peptidylarginine deiminase-mediated post-translational citrullination in pathogenesis of sporadic Creutzfeldt-Jakob disease
| Autor: | Akihito Ishigami, Jae-Kwang Jin, Richard I. Carp, Eun-Kyoung Choi, Yong-Chul Jeon, Byungki Jang, Kyung-Chan Choi, Yong-Sun Kim, Naoki Maruyama, Han Jeong Cho |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Hydrolases Blotting Western Enolase Fluorescent Antibody Technique Vimentin Protein citrullination Creutzfeldt-Jakob Syndrome Pathology and Forensic Medicine Pathogenesis Cellular and Molecular Neuroscience chemistry.chemical_compound Protein-Arginine Deiminase Type 2 Citrulline Humans Aged Protein-Arginine Deiminases Aged 80 and over biology Glial fibrillary acidic protein Citrullination Middle Aged Immunohistochemistry Frontal Lobe Up-Regulation Enzyme Activation chemistry Astrocytes Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Immunology biology.protein Female Neurology (clinical) Protein Processing Post-Translational Biomarkers |
| Zdroj: | Acta Neuropathologica. 119:199-210 |
| ISSN: | 1432-0533 0001-6322 |
| DOI: | 10.1007/s00401-009-0625-x |
| Popis: | Peptidylarginine deiminases (PADs)-mediated post-translational citrullination processes play key roles in protein functions and structural stability through the conversion of arginine to citrulline in the presence of excessive calcium concentrations. In brain, PAD2 is abundantly expressed and can be involved in citrullination in disease. Recently, we have reported pathological characterization of PAD2 and citrullinated proteins in scrapie-infected mice, but the implication of protein citrullination in the pathophysiology in human prion disease is not clear. In the present study, we explored the molecular and biological involvement of PAD2 and the pathogenesis of citrullinated proteins in frontal cortex of patients with sporadic Creutzfeldt-Jakob disease (sCJD). We found increased expression of PAD2 in reactive astrocytes that also contained increased levels of citrullinated proteins. In addition, PAD activity was significantly elevated in patients with sCJD compared to controls. From two-dimensional gel electrophoresis and MALDI-TOF mass analysis, we found various citrullinated candidates, including cytoskeletal and energy metabolism-associated proteins such as vimentin, glial fibrillary acidic protein, enolase, and phosphoglycerate kinase. Based on these findings, our investigations suggest that PAD2 activation and aberrant citrullinated proteins could play a role in pathogenesis and have value as a marker for the postmortem classification of neurodegenerative diseases. |
| Databáze: | OpenAIRE |
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