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Apoptosis induced by Aβ25-35 peptide is Ca(2+) -IP3 signaling-dependent in murine astrocytes

Oseki, K T ; Monteforte, P T ; Pereira, G J S ; Hirata, H ; Ureshino, R P ; Bincoletto, C ; Hsu, Y-T ; Smaili, S S

The European journal of neuroscience, 2014-08, Vol.40 (3), p.2471 [Periódico revisado por pares]

France

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Título:
Apoptosis induced by Aβ25-35 peptide is Ca(2+) -IP3 signaling-dependent in murine astrocytes
Autor: Oseki, K T ; Monteforte, P T ; Pereira, G J S ; Hirata, H ; Ureshino, R P ; Bincoletto, C ; Hsu, Y-T ; Smaili, S S
Assuntos: Alzheimer Disease - metabolism ; Amyloid beta-Peptides - pharmacology ; Animals ; Apoptosis - drug effects ; Astrocytes - drug effects ; Astrocytes - metabolism ; Calcium Signaling - drug effects ; Cells, Cultured ; Endoplasmic Reticulum - drug effects ; Endoplasmic Reticulum - metabolism ; Inositol 1,4,5-Trisphosphate Receptors - metabolism ; Peptide Fragments - pharmacology ; Rats ; Signal Transduction
É parte de: The European journal of neuroscience, 2014-08, Vol.40 (3), p.2471
Descrição: Although the accumulation of the neurotoxic peptide β-amyloid (Aβ) in the central nervous system is a hallmark of Alzheimer's disease, whether Aβ acts in astrocytes is unclear, and downstream functional consequences have yet to be defined. Here, we show that cytosolic Ca(2+) dysregulation, induced by a neurotoxic fragment (Aβ25-35), caused apoptosis in a concentration-dependent manner, leading to cytoplasmic Ca(2+) mobilization from extra- and intracellular sources, mainly from the endoplasmic reticulum (ER) via IP3 receptor activation. This mechanism was related to Aβ-mediated apoptosis by the intrinsic pathway because the expression of pro-apoptotic Bax was accompanied by its translocation in cells transfected with GFP-Bax. Aβ-mediated apoptosis was reduced by BAPTA-AM, a fast Ca(2+) chelator, indicating that an increase in intracellular Ca(2+) was involved in cell death. Interestingly, the Bax translocation was dependent on Ca(2+) mobilization from IP3 receptors because pre-incubation with xestospongin C, a selective IP3 receptor inhibitor, abolished this response. Taken together, these results provide evidence that Aβ dysregulation of Ca(2+) homeostasis induces ER depletion of Ca(2+) stores and leads to apoptosis; this mechanism plays a significant role in Aβ apoptotic cell death and might be a new target for neurodegeneration treatments.
Editor: France
Idioma: Inglês

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Apoptosis induced by Aβ25-35 peptide is Ca(2+) -IP3 signaling-dependent in murine astrocytes

Oseki, K T ; Monteforte, P T ; Pereira, G J S ; Hirata, H ; Ureshino, R P ; Bincoletto, C ; Hsu, Y-T ; Smaili, S S

France

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