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学科主题: 临床医学
题名:
Inhibition of VDAC1 prevents Ca2+-mediated oxidative stress and apoptosis induced by 5-aminolevulinic acid mediated sonodynamic therapy in THP-1 macrophages
作者: Chen, Haibo1; Gao, Weiwei2; Yang, Yang1; Guo, Shuyuan1; Wang, Huan1; Wang, Wei1; Zhang, Shuisheng3; Zhou, Qi4,5; Xu, Haobo1; Yao, Jianting1; Tian, Zhen2; Li, Bicheng1; Cao, Wenwu6; Zhang, Zhiguo4,5; Tian, Ye1,2
关键词: Sonodynamic therapy ; Macrophage ; Apoptosis ; Voltage-dependent anion channel 1 ; Reactive oxygen species ; Calcium
刊名: APOPTOSIS
发表日期: 2014-12-01
DOI: 10.1007/s10495-014-1045-5
卷: 19, 期:12, 页:1712-1726
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]: DEPENDENT ANION CHANNEL ; CYTOCHROME-C RELEASE ; PERMEABILITY TRANSITION PORE ; TRANSLOCATOR-PROTEIN TSPO ; CELL-DEATH ; PHOTODYNAMIC THERAPY ; OUTER-MEMBRANE ; MITOCHONDRIA ; ATHEROSCLEROSIS ; CARDIOLIPIN
英文摘要:

Ultrasound combined with endogenous protoporphyrin IX derived from 5-aminolevulinic acid (ALA-SDT) is known to induce apoptosis in multiple cancer cells and macrophages. Persistent retention of macrophages in the plaque has been implicated in the pathophysiology and progression of atherosclerosis. Here we investigated the effects of inhibition of voltage-dependent anion channel 1 (VDAC1) on ALA-SDT-induced THP-1 macrophages apoptosis. Cells were pre-treated with VDAC1 inhibitor 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) disodium salt for 1 h or downregulated VDAC1 expression by small interfering RNA and exposed to ultrasound. Cell viability was assessed by MTT assay, and cell apoptosis along with necrosis was evaluated by Hoechst 33342/propidium iodide staining and flow cytometry. Levels of cytochrome c release was assessed by confocal microscope and Western blot. The levels of full length caspases, caspase activation, and VDAC isoforms were analyzed by Western blot. Intracellular reactive oxygen species generation, mitochondrial membrane permeability, and intracellular Ca2+ [Ca2+](i) levels were measured with fluorescent probes. We confirmed that the pharmacological inhibition of VDAC1 by DIDS notably prevented ALA-SDT-induced cell apoptosis in THP-1 macrophages. Additionally, DIDS significantly inhibited intracellular ROS generation and apoptotic biochemical changes such as inner mitochondrial membrane permeabilization, loss of mitochondrial membrane potential, cytochrome c release and activation of caspase-3 and caspase-9. Moreover, ALA-SDT elevated the [Ca2+](i) levels and it was also notably reduced by DIDS. Furthermore, both of intracellular ROS generation and cell apoptosis were predominately inhibited by Ca2+ chelating reagent BAPTA-AM. Intriguingly, ALA-treatment markedly augmented VDAC1 protein levels exclusively, and the downregulation of VDAC1 expression by specific siRNA also significantly abolished cell apoptosis. Altogether, these results suggest that VDAC1 plays a crucial role in ALA-SDT-induced THP-1 macrophages apoptosis, and targeting VDAC1 is a potential way regulating macrophages apoptosis, a finding that may be relevant to therapeutic strategies against atherosclerosis.

语种: 英语
所属项目编号: 81101164 ; 81171483 ; 81371709 ; GC10C306
项目资助者: National Natural Science Foundation of China ; Scientific and Technical Key Task of Heilongjiang Province, China ; National key clinical specialist construction Programs of China
WOS记录号: WOS:000345003800005
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52306
Appears in Collections:北京大学第一临床医学院_期刊论文

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作者单位: 1.Harbin Med Univ, Affiliated Hosp 1, Dept Cardiol, Cardiovasc Inst, Harbin 150001, Heilongjiang, Peoples R China
2.Harbin Med Univ, State Prov Key Labs Biomed Pharmaceut China, Key Lab Cardiovasc Res, Dept Pathophysiol,Minist Educ, Harbin 150081, Heilongjiang, Peoples R China
3.Peking Univ, Hosp 1, Dept Intervent Radiol & Vasc Surg, Beijing 100034, Peoples R China
4.Harbin Inst Technol, Lab Photo & Sono Theranost Technol, Harbin 150081, Heilongjiang, Peoples R China
5.Harbin Inst Technol, Condensed Matter Sci & Technol Inst, Harbin 150081, Heilongjiang, Peoples R China
6.Penn State Univ, Mat Res Inst, University Pk, PA 16802 USA

Recommended Citation:
Chen, Haibo,Gao, Weiwei,Yang, Yang,et al. Inhibition of VDAC1 prevents Ca2+-mediated oxidative stress and apoptosis induced by 5-aminolevulinic acid mediated sonodynamic therapy in THP-1 macrophages[J]. APOPTOSIS,2014,19(12):1712-1726.
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