期刊
LIFE SCIENCES
卷 90, 期 19-20, 页码 808-814出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2012.04.004
关键词
Synaptic; Nonsynaptic; Mitochondria; Ca2+; ROS production; Membrane potential
资金
- Thailand Research Fund [RTA 5280006, BRG 5480003]
- Chiang Mai University
Aims: Since variety in response to Ca2+-induced mitochondrial dysfunction in different neuronal mitochondrial populations is associated with the pathogenesis of several neurological diseases, we investigated the effects of Ca2+ overload on synaptic (SM) and nonsynaptic mitochondrial (NM) dysfunction and probed the effects of cyclosporin A (CsA), 4'-chlorodiazepam (CDP) and Ru360 on relieving mitochondria! damage. Main methods: SM and NM mitochondria were isolated from rats' brains (n = 5/group) and treated with various concentrations (5, 10, 100, and 200 mu M) of Ca2+, with and without CsA (mPTP blocker), CDP (PBR/TSPO blocker) and Ru360 (MCU blocker) pretreatments. Mitochondrial function was determined by mitochondria, swelling, ROS production and mitochondrial membrane potential changes (Delta Psi m). Key findings: At 200-mu M Ca2+, SM presented mitochondrial swelling to a greater extent than NM. At 100 and 200-uM Ca2+, the ROS production of SM was higher than that of NM and Delta Psi m dissipation of SM was also larger. CsA, CDP and Ru360 could reduce ROS production of SM and NM with exposure to 200-mu M Ca2+. However, only Ru360 could completely inhibit ROS generation in both SM and NM, whereas CsA and CDP could only partially reduce the ROS level in SM. Moreover, CsA and CDP pretreatments were not able to restore Delta Psi m. However, Ru360 pretreatment could protect Delta Psi m dissipation in both SM and NM, with complete protection observed only in NM. Significance: Our findings suggested that mitochondrial calcium uniporter is a possible major pathway for calcium uptake in both mitochondrial populations. However, SM might have additional pathways involved in the calcium uptake. (C) 2012 Elsevier Inc. All rights reserved.
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