Eosinophil-induced neurotoxicity: the role of eosinophil cationic protein/RNase 3.
We analyze the effect of ECP on primary cultures of cerebellar granule cells (CGCs) and astrocytes in an effort to understand the role of ECP in the eosinophil-induced neurotoxicity. We have shown that ECP induces dose-dependent cell death in both CGCs and astrocytes. The effect of ECP action on cell morphology is consistent with apoptosis for both cell types. The apoptotic mechanism involves ECP binding on the cell surface and an increase in the free cytosolic Ca(2+) concentration. It is associated with the activation of caspase-3, -8 and -9, processes that are also involved in the apoptosis induced either by stroke or other neurodegenerative conditions. Our results open new insights to clarify the neurotoxic effects associated to ECP in the hypereosinophilic syndrome.
Navarro
Susanna
S
Departament de Bioquímica i Biologia Molecular, Facultat de Biociències, Universitat Autònoma de Barcelona, 08193-Bellaterra, Spain.
Boix
Ester
E
Cuchillo
Claudi M
CM
Nogués
M Victòria
MV
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000502:physiology / Q000633:toxicity; D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D002531:Cerebellum / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D004306:Dose-Response Relationship, Immunologic; D047150:Eosinophil Cationic Protein / Q000502:physiology* / Q000633:toxicity; D004804:Eosinophils / Q000201:enzymology* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D009498:Neurotoxins / Q000633:toxicity; D051381:Rats
D051017:Apoptosis Regulatory Proteins; D009498:Neurotoxins; D047150:Eosinophil Cationic Protein