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多糖通过ROS-Drp1信号通路减轻六价铬诱导的DF-1细胞凋亡。

Polysaccharides Alleviate Cr(VI)-Induced Apoptosis in DF-1 Cells via ROS-Drp1 Signal Pathway.

作者信息

Zhang Zhuanglong, Zheng Pimiao, Qi Changxi, Cui Yuehui, Qi Yijian, Xue Kun, Yan Guangwei, Liu Jianzhu

机构信息

College of Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, China.

Research Center for Animal Disease Control Engineering, Shandong Agricultural University, Tai'an 271018, China.

出版信息

Life (Basel). 2022 Dec 19;12(12):2144. doi: 10.3390/life12122144.

DOI:10.3390/life12122144
PMID:36556509
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9788446/
Abstract

Hexavalent chromium (Cr(VI)) is a widespread heavy metal that has been identified as a human carcinogen, and acute or chronic exposure to Cr(VI) can cause organ damage. polysaccharide (PGPS) is a constituent extracted from the Chinese herb , which has various pharmacological effects. Therefore, the author investigated the role of PGPSt in Cr(VI)-induced apoptosis in chicken embryo fibroblast cell lines (DF-1 cells). Firstly, this study infected DF-1 cells using Cr(VI) to set up a model for cytotoxicity and then added PGPSt. Then, the intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and apoptosis rate were evaluated. The results showed that PGPSt could inhibit Cr(VI)-induced mitochondrial damage and increase the apoptosis rate. For further exploration of the mechanism of regulation of PGPSt, the ROS-Drp1 pathway was investigated. The antioxidant N-acetyl-L-cysteine (NAC) and mitochondrial division inhibitor 1(Mdivi-1) were added, respectively. The results showed that the NAC and Mdivi-1 restored abnormal mitochondrial fission and cell apoptosis. Thus, PGPSt can alleviate Cr(VI)-induced apoptosis of DF-1 cells through the ROS-Drp1 signaling pathway, which may suggest new research ideas for developing new drugs to alleviate Cr(VI) toxicity.

摘要

六价铬(Cr(VI))是一种广泛存在的重金属,已被确认为人类致癌物,急性或慢性接触Cr(VI)会导致器官损伤。 多糖(PGPS)是从一种中草药中提取的成分,具有多种药理作用。因此,作者研究了PGPSt在Cr(VI)诱导的鸡胚成纤维细胞系(DF-1细胞)凋亡中的作用。首先,本研究用Cr(VI)感染DF-1细胞以建立细胞毒性模型,然后添加PGPSt。然后,评估细胞内活性氧(ROS)、线粒体膜电位(MMP)和凋亡率。结果表明,PGPSt可以抑制Cr(VI)诱导的线粒体损伤并提高凋亡率。为了进一步探索PGPSt的调控机制,研究了ROS-Drp1途径。分别添加抗氧化剂N-乙酰-L-半胱氨酸(NAC)和线粒体分裂抑制剂1(Mdivi-1)。结果表明,NAC和Mdivi-1恢复了异常的线粒体分裂和细胞凋亡。因此,PGPSt可以通过ROS-Drp1信号通路减轻Cr(VI)诱导的DF-1细胞凋亡,这可能为开发减轻Cr(VI)毒性的新药提供新的研究思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0289/9788446/cf5b7950cc79/life-12-02144-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0289/9788446/b9d5f1ced163/life-12-02144-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0289/9788446/b7ad208a4d25/life-12-02144-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0289/9788446/884acb00633e/life-12-02144-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0289/9788446/cf5b7950cc79/life-12-02144-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0289/9788446/b9d5f1ced163/life-12-02144-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0289/9788446/b7ad208a4d25/life-12-02144-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0289/9788446/884acb00633e/life-12-02144-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0289/9788446/cf5b7950cc79/life-12-02144-g004.jpg

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本文引用的文献

1
Long-term hexavalent chromium exposure disturbs the gut microbial homeostasis of chickens.长期六价铬暴露会扰乱鸡的肠道微生物稳态。
Ecotoxicol Environ Saf. 2022 Jun 1;237:113532. doi: 10.1016/j.ecoenv.2022.113532. Epub 2022 Apr 23.
2
Inhibition of Sirtuin-1 hyperacetylates p53 and abrogates Sirtuin-1-p53 interaction in Cr(VI)-induced apoptosis in the ovary.在 Cr(VI)诱导的卵巢细胞凋亡中,Sirtuin-1 的过度乙酰化抑制了 p53,并破坏了 Sirtuin-1-p53 的相互作用。
Reprod Toxicol. 2022 Apr;109:121-134. doi: 10.1016/j.reprotox.2022.03.007. Epub 2022 Mar 17.
3
The role of microRNAs in regulating cadmium-induced apoptosis by targeting Bcl-2 in IEC-6 cells.
微小 RNA 在调节镉诱导的 IEC-6 细胞凋亡中的作用及其对 Bcl-2 的靶向调控。
Toxicol Appl Pharmacol. 2021 Dec 1;432:115737. doi: 10.1016/j.taap.2021.115737. Epub 2021 Oct 16.
4
Platycodon grandiflorus polysaccharides inhibit Pseudorabies virus replication via downregulating virus-induced autophagy.桔梗多糖通过下调病毒诱导的自噬抑制伪狂犬病病毒复制。
Res Vet Sci. 2021 Nov;140:18-25. doi: 10.1016/j.rvsc.2021.08.004. Epub 2021 Aug 8.
5
Genome wide profiling of miRNAs relevant to the DNA damage response induced by hexavalent chromium exposure (DDR-related miRNAs in response to Cr (VI) exposure).与六价铬暴露诱导的DNA损伤反应相关的微小RNA的全基因组分析(响应Cr(VI)暴露的DDR相关微小RNA)
Environ Int. 2021 Dec;157:106782. doi: 10.1016/j.envint.2021.106782. Epub 2021 Jul 28.
6
Reduced Levels of Drp1 Protect against Development of Retinal Vascular Lesions in Diabetic Retinopathy.Drp1 水平降低可预防糖尿病视网膜病变中的视网膜血管病变。
Cells. 2021 Jun 3;10(6):1379. doi: 10.3390/cells10061379.
7
Clusterin inhibits Cr(VI)-induced apoptosis via enhancing mitochondrial biogenesis through AKT-associated STAT3 activation in L02 hepatocytes.簇集蛋白通过 AKT 相关 STAT3 激活增强线粒体生物发生来抑制 Cr(VI)诱导的 L02 肝细胞凋亡。
Ecotoxicol Environ Saf. 2021 Sep 15;221:112447. doi: 10.1016/j.ecoenv.2021.112447. Epub 2021 Jun 25.
8
Characterization of an antioxidant pectic polysaccharide from Platycodon grandiflorus.白花前胡中一种抗氧化的果胶多糖的特性研究。
Int J Biol Macromol. 2021 Apr 1;175:473-480. doi: 10.1016/j.ijbiomac.2021.02.041. Epub 2021 Feb 8.
9
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J Hazard Mater. 2021 May 15;410:124607. doi: 10.1016/j.jhazmat.2020.124607. Epub 2020 Nov 19.
10
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Mol Med Rep. 2021 Jan;23(1). doi: 10.3892/mmr.2020.11653. Epub 2020 Nov 12.