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 Ca(2+) 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 Ca(2+), 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.
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Authors | Tuo Ma, Kai Gong, Yufang Yan, Bo Song, Xiufang Zhang, Yandao Gong |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 426
Issue 2
Pg. 196-202
(Sep 21 2012)
ISSN: 1090-2104 [Electronic] United States |
PMID | 22935417
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Inc. All rights reserved. |
Chemical References |
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Topics |
- Alzheimer Disease
(metabolism)
- Animals
- Calcium
(metabolism)
- Cell Line
- Homeostasis
- Humans
- Mice
- Mice, Transgenic
- Mitochondria
(metabolism)
- Models, Biological
- Neurons
(metabolism)
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