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Journal of Zhejiang University SCIENCE B 2018 Vol.19 No.6 P.425-435

http://doi.org/10.1631/jzus.B1700488


NF-κB in mitochondria regulates PC12 cell apoptosis following lipopolysaccharide-induced injury


Author(s):  Ying Song, Zhuo-Chao Wu, Wei Ding, Yun Bei, Zhi-Yun Lin

Affiliation(s):  Department of Pharmacology, Zhejiang University of Technology, Hangzhou 310014, China; more

Corresponding email(s):   songying@zjut.edu.cn

Key Words:  Nuclear transcription factor κ, B (NF-κ, B), Mitochondria, Apoptosis, Adenine nucleotide translocase 1 (ANT1), Lipopolysaccharide (LPS)


Ying Song, Zhuo-Chao Wu, Wei Ding, Yun Bei, Zhi-Yun Lin. NF-κB in mitochondria regulates PC12 cell apoptosis following lipopolysaccharide-induced injury[J]. Journal of Zhejiang University Science B, 2018, 19(6): 425-435.

@article{title="NF-κB in mitochondria regulates PC12 cell apoptosis following lipopolysaccharide-induced injury",
author="Ying Song, Zhuo-Chao Wu, Wei Ding, Yun Bei, Zhi-Yun Lin",
journal="Journal of Zhejiang University Science B",
volume="19",
number="6",
pages="425-435",
year="2018",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1700488"
}

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%T NF-κB in mitochondria regulates PC12 cell apoptosis following lipopolysaccharide-induced injury
%A Ying Song
%A Zhuo-Chao Wu
%A Wei Ding
%A Yun Bei
%A Zhi-Yun Lin
%J Journal of Zhejiang University SCIENCE B
%V 19
%N 6
%P 425-435
%@ 1673-1581
%D 2018
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1700488

TY - JOUR
T1 - NF-κB in mitochondria regulates PC12 cell apoptosis following lipopolysaccharide-induced injury
A1 - Ying Song
A1 - Zhuo-Chao Wu
A1 - Wei Ding
A1 - Yun Bei
A1 - Zhi-Yun Lin
J0 - Journal of Zhejiang University Science B
VL - 19
IS - 6
SP - 425
EP - 435
%@ 1673-1581
Y1 - 2018
PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B1700488


Abstract: 
Objective: To determine the relationship between nuclear transcription factor κ;b (NF-κ;b) expression in mitochondria and neuronal cell apoptosis after lipopolysaccharide (LPS)-induced injury. Methods: The effect of drug administration on PC12 cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Hoechst 33342 staining. The morphology and function of mitochondria were investigated with electron microscopy and rhodamine 123, respectively. The activity of adenine nucleotide translocase 1 (ANT1), lipid peroxide, and anti-peroxidase enzymes was measured by enzyme-linked immunosorbent assay (ELISA). Relative expression levels of NF-κB were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Results: Pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) and nerve growth factor (NGF) not only reduced apoptosis but also had a protective effect on mitochondrial structure and function in a PC12 cell LPS damage model. The subcellular distribution of NF-κB demonstrated that NGF, diterpene acid atractyloside (ATR, an ANT1 antagonist), and PDTC alleviated increases in mitochondrial NF-κB after LPS-induced injury. Conclusions: (1) NF-κB is activated in mitochondria via uptake of ANT1 during apoptosis following LPS-induced injury in neuronal cells; (2) NGF not only decreases the activity of NF-κB but also reduces ANT1 activity, which in turn decreases NF-κB levels in mitochondria and suppresses mitochondria-mediated apoptosis.

线粒体中的NF-κB调节脂多糖诱导损伤后PC12细胞的凋亡

目的:探讨线粒体内核转录因子(NF-κB)的表达与脂多糖(LPS)诱导损伤后神经细胞的凋亡之间的关系.
创新点:(1)LPS诱导后,线粒体中NF-κB的增加导致细胞凋亡;(2)腺嘌呤核苷酸转位酶1(ANT1)活性决定线粒体中NF-κB的水平.
方法:通过MTT和Hoechst 33342染色来测定药物对PC12细胞的作用;用电子显微镜和罗丹明123(rhodamine 123)检测线粒体的形态和功能;通过酶联免疫吸附测定(ELISA)测量ANT1、脂质过氧化物和抗过氧化物酶的活性;反转录聚合酶链反应(RT-PCR)和蛋白质印迹法(Western blot)检测NF-κB的相对表达水平.
结论:(1)在LPS诱导的神经元细胞损伤后的细胞凋亡期间,NF-κB通过摄取ANT1在线粒体中被激活;(2)神经生长因子(NGF)不仅降低NF-κB活性,还降低ANT1活性,进而使得线粒体中NF-κB的表达水平下降,并抑制线粒体介导的细胞凋亡.

关键词:核转录因子(NF-κB);线粒体;细胞凋亡;腺嘌呤核苷酸转位酶1(ANT1);脂多糖(LPS)

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