Full Text:   <407>

Summary:  <140>

CLC number: R73-3

On-line Access: 2019-04-01

Received: 2018-06-07

Revision Accepted: 2018-11-15

Crosschecked: 2019-03-02

Cited: 0

Clicked: 734

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Hui Pan

https://orcid.org/0000-0002-8697-816X

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Journal of Zhejiang University SCIENCE B 2019 Vol.20 No.4 P.310-321

http://doi.org/10.1631/jzus.B1800319


Mitochondrial superoxide anions induced by exogenous oxidative stress determine tumor cell fate: an individual cell-based study


Author(s):  Hui Pan, Bao-hui Wang, Zhou-bin Li, Xing-guo Gong, Yong Qin, Yan Jiang, Wei-li Han

Affiliation(s):  The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China; more

Corresponding email(s):   phwbhpxc@zju.edu.cn, wang.baohui888@163.com, zjhzhwldoc@zju.edu.cn

Key Words:  Individual cell, Superoxide anion, Reactive oxygen species (ROS) dynamics, Intrinsic apoptotic pathway, Ca2+ signaling


Hui Pan, Bao-hui Wang, Zhou-bin Li, Xing-guo Gong, Yong Qin, Yan Jiang, Wei-li Han. Mitochondrial superoxide anions induced by exogenous oxidative stress determine tumor cell fate: an individual cell-based study[J]. Journal of Zhejiang University Science B, 2019, 20(4): 310-321.

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author="Hui Pan, Bao-hui Wang, Zhou-bin Li, Xing-guo Gong, Yong Qin, Yan Jiang, Wei-li Han",
journal="Journal of Zhejiang University Science B",
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pages="310-321",
year="2019",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1800319"
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%T Mitochondrial superoxide anions induced by exogenous oxidative stress determine tumor cell fate: an individual cell-based study
%A Hui Pan
%A Bao-hui Wang
%A Zhou-bin Li
%A Xing-guo Gong
%A Yong Qin
%A Yan Jiang
%A Wei-li Han
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A1 - Hui Pan
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A1 - Zhou-bin Li
A1 - Xing-guo Gong
A1 - Yong Qin
A1 - Yan Jiang
A1 - Wei-li Han
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B1800319


Abstract: 
Objective: Reactive oxygen species (ROS) are involved in a variety of biological phenomena and serve both deleterious and beneficial roles. ROS quantification and assessment of reaction networks are desirable but difficult because of their short half-life and high reactivity. Here, we describe a pro-oxidative model in a single human lung carcinoma SPC-A-1 cell that was created by application of extracellular H2O2 stimuli. Methods: Modified microfluidics and imaging techniques were used to determine O2•− levels and construct an O2•− reaction network. To elucidate the consequences of increased O2•− input, the mitochondria were given a central role in the oxidative stress mode, by manipulating mitochondria-interrelated cytosolic Ca2+ levels, mitochondrial Ca2+ uptake, auto-amplification of intracellular ROS and the intrinsic apoptotic pathway. Results and conclusions: Results from a modified microchip demonstrated that 1 mmol/L H2O2 induced a rapid increase in cellular O2•− levels (>27 vs. >406 amol in 20 min), leading to increased cellular oxidizing power (evaluated by ROS levels) and decreased reducing power (evaluated by glutathione (GSH) levels). In addition, we examined the dynamics of cytosolic Ca2+ and mitochondrial Ca2+ by confocal laser scanning microscopy and confirmed that Ca2+ stores in the endoplasmic reticulum were the primary source of H2O2-induced cytosolic Ca2+ bursts. It is clear that mitochondria have pivotal roles in determining how exogenous oxidative stress affects cell fate. The stress response involves the transfer of Ca2+ signals between organelles, ROS auto-amplification, mitochondrial dysfunction, and a caspase-dependent apoptotic pathway.

外源性氧化应激诱导的线粒体超氧阴离子决定肿瘤细胞命运:一项基于单个细胞的研究

目的:通过细胞外过氧化氢(H2O2)的刺激建立单个人肺癌SPC-A-1细胞的氧化压力模型.
创新点:氧自由基(ROS)涉及多种生物现象,包括有益和有害两个方面.ROS的定量检测和反应网络的评估结果令人期待.但ROS半衰期很短且反应过程很快,因此,我们通过多种手段克服了检测和评估的困难.
方法:利用改进的微流控和成像技术测定ROS水平,构建氧反应网络.通过调控线粒体胞浆Ca2+水平、线粒体Ca2+摄取、细胞内ROS自扩增以及内在凋亡途径,确定线粒体在外源氧化压力模式中扮演的角色.
结论:研究结果表明1 mmol/L H2O2引起细胞O2•−水平的快速增加,从而导致细胞氧化能力增加和还原能力降低.此外,研究还证实了内质网中储存的Ca2+是H2O2诱导的线粒体Ca2+爆发的主要来源.外源氧化压力反应涉及细胞器间Ca2+信号的传递、ROS自身扩增、线粒体功能紊乱和半胱天冬酶依赖性凋亡途径.线粒体在外源性氧化应激影响细胞命运方面发挥着关键作用.

关键词:单个细胞;超氧阴离子;氧自由基动力学;内源性凋亡途径;钙信号

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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