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Mitochondrial modulation of store-operated Ca2+ entry in model cells of Alzheimer’s disease
- Source :
-
Biochemical & Biophysical Research Communications . Sep2012, Vol. 426 Issue 2, p196-202. 7p. - Publication Year :
- 2012
-
Abstract
- Abstract: Mitochondrial malfunction and calcium dyshomeostasis are early pathological events considered as important features of the Alzheimer’s disease (AD) brain. Recent studies have suggested mitochondrion as an active regulator of Ca2+ signaling based on its calcium buffering capacity. Herein, we investigated the mitochondrial involvement in the modulation of store-operated calcium entry (SOCE) in neural 2a (N2a) transgenic AD model cells. Results showed that SOCE was significantly depressed in N2a cells transfected with wild-type human APP695 (N2a APPwt) compared with empty vector control (N2a WT) cells. Pharmacological manipulation with mitochondrial function blockers, such as FCCP, RuR, or antimycin A/oligomycin, could inhibit mitochondrial calcium handling, and then impair SOCE pathway in N2a WT cells. Furthermore, mitochondria of N2a APPwt cells exhibited more severe swelling in response to Ca2+, which is an indication of mitochondrial membrane permeability transition (MPT), than the wild-type controls. Additionally, treatment with cyclosporin A, a potent inhibitor of cyclophilin D, which can block MPT, could significantly restore the attenuated SOCE in N2a APPwt cells. Therefore, inhibition of cyclophilin D might be a therapeutic strategy for Alzheimer’s disease. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 426
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 80187829
- Full Text :
- https://doi.org/10.1016/j.bbrc.2012.08.062