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CLC number: Q25

On-line Access: 2018-06-04

Received: 2017-03-15

Revision Accepted: 2017-06-12

Crosschecked: 2018-05-14

Cited: 0

Clicked: 1734

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Qing-hua Cui

https://orcid.org/0000-0002-1725-8046

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Journal of Zhejiang University SCIENCE B 2018 Vol.19 No.6 P.415-424

http://doi.org/10.1631/jzus.B1700148


PGC-1α coordinates with Bcl-2 to control the cell cycle in U251 cells through reducing ROS


Author(s):  Kun Yao, Xu-feng Fu, Xing Du, Yan Li, Shan-shan Yang, Min Yu, Qing-hua Cui

Affiliation(s):  School of Life Sciences, Yunnan University, Kunming 650091, China; more

Corresponding email(s):   cuiqinghua@ynu.edu.cn

Key Words:  B-cell lymphoma 2 (Bcl-2), Peroxisome proliferator-activated receptor-γ, co-activator 1α, (PGC-1α, ), Mitochondria, Reactive oxygen species (ROS), Cell cycle


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Kun Yao, Xu-feng Fu, Xing Du, Yan Li, Shan-shan Yang, Min Yu, Qing-hua Cui. PGC-1α coordinates with Bcl-2 to control the cell cycle in U251 cells through reducing ROS[J]. Journal of Zhejiang University Science B, 2018, 19(6): 415-424.

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author="Kun Yao, Xu-feng Fu, Xing Du, Yan Li, Shan-shan Yang, Min Yu, Qing-hua Cui",
journal="Journal of Zhejiang University Science B",
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publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1700148"
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%T PGC-1α coordinates with Bcl-2 to control the cell cycle in U251 cells through reducing ROS
%A Kun Yao
%A Xu-feng Fu
%A Xing Du
%A Yan Li
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%A Min Yu
%A Qing-hua Cui
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%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1700148

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T1 - PGC-1α coordinates with Bcl-2 to control the cell cycle in U251 cells through reducing ROS
A1 - Kun Yao
A1 - Xu-feng Fu
A1 - Xing Du
A1 - Yan Li
A1 - Shan-shan Yang
A1 - Min Yu
A1 - Qing-hua Cui
J0 - Journal of Zhejiang University Science B
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B1700148


Abstract: 
B-cell lymphoma 2 (Bcl-2) has a dual function, acting as both an oncogene and an anti-tumor gene. It is well known that Bcl-2 exerts its tumor promoting function through the mitochondrial pathway. However, the mechanism by which it suppresses tumor formation is not well understood. We have previously shown that Bcl-2 inhibits cell cycle progression from the G0/G1 to the S phase after serum starvation, and that quiescent Bcl-2 expressing cells maintain a significantly lower level of mitochondrial reactive oxygen species (ROS) than control cells. Based on the fact that ROS mediate cell cycle progression and are controlled by peroxisome proliferator-activated receptor-γ; co-activator 1α; (PGC-1α;), a key molecule induced by prolonged starvation and involved in mitochondrial metabolism, we hypothesized that PGC-1α might be related to the cell cycle function of Bcl-2. In this paper, we show that PGC-1α is upregulated by Bcl-2 overexpression and downregulated following Bcl-2 knockdown or downregulation after serum starvation. However, Bcl-2 is negatively regulated by PGC-1α expression. Further, co-immunoprecipitation (co-IP) experiments showed that PGC-1α protein is co-precipitated with Bcl-2 at the G0/G1 phase. Taken together, our results suggest that PGC-1α interacts with Bcl-2 after serum depletion, and that Bcl-2 might recruit PGC-1α to reduce ROS, which in turn delays cell cycle progression in coordination with Bcl-2.

PGC-1α在U251细胞中协同Bcl-2通过降低ROS来调控细胞周期

目的:探究过氧化物酶体增生激活受体γ协同刺激因子1α (PGC-1α)和B细胞淋巴瘤-2(Bcl-2)在调控细胞周期中的相互关系.
创新点:首次证明在血清饥饿时PGC-1α负调控Bcl-2,并且认为Bcl-2可能通过招募PGC-1α降低细胞中的活性氧自由基(ROS)以调节细胞周期.
方法:用蛋白质印迹法(Western blotting)检测了接触抑制和血清饥饿处理的NIH3T3过表达Bcl-2的细胞中PGC-1α的表达,并且分别检测了用Bcl-2和PGC-1α的小干扰RNA(siRNA)降低U251细胞(内源性高表达Bcl-2和PGC-1α)中的Bcl-2和PGC-1α的表达,最后用免疫共沉淀(co-IP)检测了二者的关系.
结论:本实验中用两种细胞同步化的方法(接触抑制和血清饥饿)处理了Bcl-2过表达的NIH3T3细胞时发现PGC-1α高表达,用Bcl-2的siRNA处理了U251细胞时发现PGC-1α的表达降低,但是血清饥饿处理了U251后发现Bcl-2升高而PGC-1α降低,而且PGC-1α被siRNA降低后Bcl-2反而上升,最后用Bcl-2抗体免疫共沉淀了PGC-1α蛋白,这些结果说明在血清饥饿时PGC-1α负调控Bcl-2行使调节细胞周期的功能.

关键词:过氧化物酶体增生激活受体γ协同刺激因子1α (PGC-1α);B细胞淋巴瘤-2(Bcl-2);线粒体;活性氧自由基(ROS);细胞周期

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[28]List of electronic supplementary materials

[29]Fig. S1 Immunofluorescence images of PGC-1α and Bcl-2 protein co-localization in NIH3T3 cells

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