The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway
In this study, we analyzed whether ER Ca2+ release, induced by amyloid-β (Aβ) and prion (PrP) peptides activates the mitochondrial-mediated apoptotic pathway. In cortical neurons, addition of the synthetic Aβ1–40 or PrP106–126 peptides depletes ER Ca2+ content, leading to cytosolic Ca2+ overload. Th...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2008-06-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996108000284 |
| _version_ | 1818721432132124672 |
|---|---|
| author | Elisabete Ferreiro Catarina R. Oliveira Cláudia M.F. Pereira |
| author_facet | Elisabete Ferreiro Catarina R. Oliveira Cláudia M.F. Pereira |
| author_sort | Elisabete Ferreiro |
| collection | DOAJ |
| description | In this study, we analyzed whether ER Ca2+ release, induced by amyloid-β (Aβ) and prion (PrP) peptides activates the mitochondrial-mediated apoptotic pathway. In cortical neurons, addition of the synthetic Aβ1–40 or PrP106–126 peptides depletes ER Ca2+ content, leading to cytosolic Ca2+ overload. The Ca2+ released through ryanodine (RyR) and inositol 1,4,5-trisphosphate (IP3R) receptors was shown to be involved in the loss of mitochondrial membrane potential, Bax translocation to mitochondria and apoptotic death. Our data further demonstrate that Ca2+ released from the ER leads to the depletion of endogenous GSH levels and accumulation of reactive oxygen species, which were also involved in the depolarization of the mitochondrial membrane. These results illustrate that the early Aβ- and PrP -induced perturbation of ER Ca2+ homeostasis affects mitochondrial function, activating the mitochondrial-mediated apoptotic pathway and help to clarify the mechanism implicated in neuronal death that occurs in AD and PrD. |
| first_indexed | 2024-12-17T20:38:38Z |
| format | Article |
| id | doaj.art-f25268e914d6408ab4546a19391c2997 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T20:38:38Z |
| publishDate | 2008-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-f25268e914d6408ab4546a19391c29972022-12-21T21:33:23ZengElsevierNeurobiology of Disease1095-953X2008-06-01303331342The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathwayElisabete Ferreiro0Catarina R. Oliveira1Cláudia M.F. Pereira2Center for Neuroscience and Cell Biology, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, PortugalCenter for Neuroscience and Cell Biology, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, PortugalCorresponding author. Fax: +351 239822776.; Center for Neuroscience and Cell Biology, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, PortugalIn this study, we analyzed whether ER Ca2+ release, induced by amyloid-β (Aβ) and prion (PrP) peptides activates the mitochondrial-mediated apoptotic pathway. In cortical neurons, addition of the synthetic Aβ1–40 or PrP106–126 peptides depletes ER Ca2+ content, leading to cytosolic Ca2+ overload. The Ca2+ released through ryanodine (RyR) and inositol 1,4,5-trisphosphate (IP3R) receptors was shown to be involved in the loss of mitochondrial membrane potential, Bax translocation to mitochondria and apoptotic death. Our data further demonstrate that Ca2+ released from the ER leads to the depletion of endogenous GSH levels and accumulation of reactive oxygen species, which were also involved in the depolarization of the mitochondrial membrane. These results illustrate that the early Aβ- and PrP -induced perturbation of ER Ca2+ homeostasis affects mitochondrial function, activating the mitochondrial-mediated apoptotic pathway and help to clarify the mechanism implicated in neuronal death that occurs in AD and PrD.http://www.sciencedirect.com/science/article/pii/S0969996108000284Alzheimer's diseasePrion disordersAmyloid-βpeptidePrion peptideApoptosis |
| spellingShingle | Elisabete Ferreiro Catarina R. Oliveira Cláudia M.F. Pereira The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway Neurobiology of Disease Alzheimer's disease Prion disorders Amyloid-β peptide Prion peptide Apoptosis |
| title | The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway |
| title_full | The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway |
| title_fullStr | The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway |
| title_full_unstemmed | The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway |
| title_short | The release of calcium from the endoplasmic reticulum induced by amyloid-beta and prion peptides activates the mitochondrial apoptotic pathway |
| title_sort | release of calcium from the endoplasmic reticulum induced by amyloid beta and prion peptides activates the mitochondrial apoptotic pathway |
| topic | Alzheimer's disease Prion disorders Amyloid-β peptide Prion peptide Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0969996108000284 |
| work_keys_str_mv | AT elisabeteferreiro thereleaseofcalciumfromtheendoplasmicreticuluminducedbyamyloidbetaandprionpeptidesactivatesthemitochondrialapoptoticpathway AT catarinaroliveira thereleaseofcalciumfromtheendoplasmicreticuluminducedbyamyloidbetaandprionpeptidesactivatesthemitochondrialapoptoticpathway AT claudiamfpereira thereleaseofcalciumfromtheendoplasmicreticuluminducedbyamyloidbetaandprionpeptidesactivatesthemitochondrialapoptoticpathway AT elisabeteferreiro releaseofcalciumfromtheendoplasmicreticuluminducedbyamyloidbetaandprionpeptidesactivatesthemitochondrialapoptoticpathway AT catarinaroliveira releaseofcalciumfromtheendoplasmicreticuluminducedbyamyloidbetaandprionpeptidesactivatesthemitochondrialapoptoticpathway AT claudiamfpereira releaseofcalciumfromtheendoplasmicreticuluminducedbyamyloidbetaandprionpeptidesactivatesthemitochondrialapoptoticpathway |