Endoplasmic Reticulum Stress and Neurodegeneration in Experimental Cerebral Malaria
| Autor: | Sripada Santosh Anand, Phanithi Prakash Babu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
C/EBP homologous protein (CHOP)
Fluoro-Jade B stain Cerebral malaria Neuronal cell death Protein kinase RNA-like endoplasmic reticulum kinase Phosphorylated eukaryotic initiation factor α Activating transcription factor 4 Caspase-12 Binding immunoglobulin protein Neurology. Diseases of the nervous system RC346-429 Neurophysiology and neuropsychology QP351-495 |
| Zdroj: | Neurosignals, Vol 21, Iss 1-2, Pp 99-111 (2012) |
| Druh dokumentu: | article |
| ISSN: | 1424-862X 1424-8638 |
| DOI: | 10.1159/000336970 |
| Popis: | Experimental cerebral malaria (ECM) resulting from Plasmodium berghei ANKA (PbA) infection in mice results in neuronal cell death. However, the precise mechanisms leading to neuronal cell death in ECM have not been fully elucidated. In the present study, we report the presence of endoplasmic reticulum (ER) stress markers and activation of the unfolded protein response (UPR) in the brain during the pathogenesis of ECM. Specific findings included activation of PKR-like ERkinase, inositol-requiring enzyme 1 and cleavage of activating transcription factor (ATF) 6 indicating the activation of all three major arms of the UPR. Further, we found changes in the protein levels of phosphorylated eukaryotic initiation factor α (p-eIF2α), ATF4, growth arrest and DNA damage-inducible protein 34, B cell lymphoma protein 2 (BCL-2), BCL-2-associated X protein, caspase-7, cleavage of caspase-3, and caspase-12. Our results demonstrate that ER stress-induced neuronal cell death in PbA-infected mice is associated with the expression of the pro-apoptotic molecule CHOP and downregulation of anti-apoptotic ER quality control molecules binding immunoglobulin protein, calreticulin and calnexin. Further CHOP was found to be localized in neurons and plays an essential role in neuronal cell death as revealed by our Fluoro-Jade B double staining. These results implicate an imbalance between ER stress-mediated pro-apoptotic and anti-apoptotic/survival signalling as a critical determinant of neuronal cell death in ECM. |
| Databáze: | Directory of Open Access Journals |
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