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呋喃丹加速 spns1 突变型斑马鱼的细胞衰老并缩短其寿命。

Carbofuran accelerates the cellular senescence and declines the life span of spns1 mutant zebrafish.

机构信息

Department of Pharmacy, University of Rajshahi, Rajshahi, Bangladesh.

Department of Molecular Medicine, The Scripps Research Institute, Jupiter, FL, USA.

出版信息

J Cell Mol Med. 2021 Jan;25(2):1048-1059. doi: 10.1111/jcmm.16171. Epub 2020 Dec 4.

DOI:10.1111/jcmm.16171
PMID:33277797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7812278/
Abstract

Carbofuran is a carbamate pesticide, widely used in agricultural practices to increase crop productivity. In mammals, carbofuran is known to cause several untoward effects, such as apoptosis in the hippocampal neuron, oxidative stress, loss of memory and chromosomal anomalies. Most of these effects are implicated with cellular senescence. Therefore, the present study aimed to determine the effect of carbofuran on cellular senescence and biological ageing. Spinster homolog 1 (Spns1) is a transmembrane transporter, regulates autolysosomal biogenesis and plays a role in cellular senescence and survival. Using senescence-associated β-galactosidase staining, we found that carbofuran accelerates the cellular senescence in spns1 mutant zebrafish. The yolk opaqueness, a premature ageing phenotype in zebrafish embryos, was accelerated by carbofuran treatment. In the survival study, carbofuran shortened the life span of spns1 mutant zebrafish. Autophagy is the cellular lysosomal degradation, usually up-regulated in the senescent cells. To know the impact of carbofuran exposure on autophagy progress, we established a double-transgenic zebrafish line, harbouring EGFP-tagged LC3-II and mCherry-tagged Lamp1 on spns1 mutant background, whereas we found, carbofuran exposure synergistically accelerates autolysosome formation with insufficient lysosome-mediated degradation. Our data collectively suggest that carbofuran exposure synergistically accelerates the cellular senescence and affects biological ageing in spns1 defective animals.

摘要

呋喃丹是一种氨基甲酸酯类农药,广泛应用于农业生产中以提高作物产量。在哺乳动物中,呋喃丹已知会引起多种不良反应,如海马神经元凋亡、氧化应激、记忆丧失和染色体异常。这些影响大多与细胞衰老有关。因此,本研究旨在确定呋喃丹对细胞衰老和生物老化的影响。Spns1 是一种跨膜转运蛋白,调节自噬体的生物发生,在细胞衰老和存活中发挥作用。通过衰老相关的β-半乳糖苷酶染色,我们发现呋喃丹加速了 spns1 突变型斑马鱼的细胞衰老。卵黄不透明度是斑马鱼胚胎的一种早衰表型,呋喃丹处理加速了这种表型。在生存研究中,呋喃丹缩短了 spns1 突变型斑马鱼的寿命。自噬是细胞溶酶体降解,通常在衰老细胞中上调。为了了解呋喃丹暴露对自噬进展的影响,我们建立了一个双转基因斑马鱼系,在 spns1 突变背景下携带 EGFP 标记的 LC3-II 和 mCherry 标记的 Lamp1,而我们发现,呋喃丹暴露协同加速了自噬体的形成,但溶酶体介导的降解不足。我们的数据表明,呋喃丹暴露协同加速了 spns1 缺陷动物的细胞衰老,并影响了它们的生物老化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b504/7812278/0f10eaf5aac0/JCMM-25-1048-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b504/7812278/9d4465b58951/JCMM-25-1048-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b504/7812278/570ce7fb8449/JCMM-25-1048-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b504/7812278/969300f8f5f1/JCMM-25-1048-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b504/7812278/77a257a4520a/JCMM-25-1048-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b504/7812278/ac665d90601f/JCMM-25-1048-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b504/7812278/0f10eaf5aac0/JCMM-25-1048-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b504/7812278/9d4465b58951/JCMM-25-1048-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b504/7812278/570ce7fb8449/JCMM-25-1048-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b504/7812278/969300f8f5f1/JCMM-25-1048-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b504/7812278/77a257a4520a/JCMM-25-1048-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b504/7812278/ac665d90601f/JCMM-25-1048-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b504/7812278/0f10eaf5aac0/JCMM-25-1048-g006.jpg

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本文引用的文献

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Implications of Oxidative Stress and Cellular Senescence in Age-Related Thymus Involution.氧化应激和细胞衰老对与年龄相关的胸腺萎缩的影响。
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PAI-1 contributes to homocysteine-induced cellular senescence.PAI-1 促进同型半胱氨酸诱导的细胞衰老。
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