Purine Metabolism and Pyrimidine Metabolism Alteration Is a Potential Mechanism of BDE-47-Induced Apoptosis in Marine Rotifer <i>Brachionus plicatilis</i>

This present study was conducted to provide evidence and an explanation for the apoptosis that occurs in the marine rotifer <i>Brachionus plicatilis</i> when facing 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) stress. Metabolomics analysis showed that aminoacyl-tRNA biosynthesis, valine,...

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Main Authors: Sai Cao, Jiayi Wang, Xinye You, Bin Zhou, You Wang, Zhongyuan Zhou
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/16/12726
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author Sai Cao
Jiayi Wang
Xinye You
Bin Zhou
You Wang
Zhongyuan Zhou
author_facet Sai Cao
Jiayi Wang
Xinye You
Bin Zhou
You Wang
Zhongyuan Zhou
author_sort Sai Cao
collection DOAJ
description This present study was conducted to provide evidence and an explanation for the apoptosis that occurs in the marine rotifer <i>Brachionus plicatilis</i> when facing 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) stress. Metabolomics analysis showed that aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine biosynthesis, and arginine biosynthesis were the top three sensitive pathways to BDE-47 exposure, which resulted in the reduction in the amino acid pool level. Pyrimidine metabolism and purine metabolism pathways were also significantly influenced, and the purine and pyrimidine content were obviously reduced in the low (0.02 mg/L) and middle (0.1 mg/L) concentration groups while increased in the high (0.5 mg/L) concentration group, evidencing the disorder of nucleotide synthesis and decomposition in <i>B. plicatilis</i>. The biochemical detection of the key enzymes in purine metabolism and pyrimidine metabolism showed the downregulation of Glutamine Synthetase (GS) protein expression and the elevation of Xanthine Oxidase (XOD) activity, which suggested the impaired DNA repair and ROS overproduction. The content of DNA damage biomarker (8-OHdG) increased in treatment groups, and the p53 signaling pathway was found to be activated, as indicated by the elevation of the p53 protein expression and Bax/Bcl-2 ratio. The ROS scavenger (N-acetyl-L-cysteine, NAC) addition effectively alleviated not only ROS overproduction but also DNA damage as well as the activation of apoptosis. The combined results backed up the speculation that purine metabolism and pyrimidine metabolism alteration play a pivotal role in BDE-47-induced ROS overproduction and DNA damage, and the consequent activation of the p53 signaling pathway led to the observed apoptosis in <i>B. plicatilis.</i>
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spelling doaj.art-7f39162e92ba4e67b3f7fba45b41fa592023-11-19T01:28:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124161272610.3390/ijms241612726Purine Metabolism and Pyrimidine Metabolism Alteration Is a Potential Mechanism of BDE-47-Induced Apoptosis in Marine Rotifer <i>Brachionus plicatilis</i>Sai Cao0Jiayi Wang1Xinye You2Bin Zhou3You Wang4Zhongyuan Zhou5College of Marine Life Science, Ocean University of China, Qingdao 266003, ChinaCollege of Marine Life Science, Ocean University of China, Qingdao 266003, ChinaCollege of Marine Life Science, Ocean University of China, Qingdao 266003, ChinaCollege of Marine Life Science, Ocean University of China, Qingdao 266003, ChinaCollege of Marine Life Science, Ocean University of China, Qingdao 266003, ChinaCollege of Marine Life Science, Ocean University of China, Qingdao 266003, ChinaThis present study was conducted to provide evidence and an explanation for the apoptosis that occurs in the marine rotifer <i>Brachionus plicatilis</i> when facing 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) stress. Metabolomics analysis showed that aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine biosynthesis, and arginine biosynthesis were the top three sensitive pathways to BDE-47 exposure, which resulted in the reduction in the amino acid pool level. Pyrimidine metabolism and purine metabolism pathways were also significantly influenced, and the purine and pyrimidine content were obviously reduced in the low (0.02 mg/L) and middle (0.1 mg/L) concentration groups while increased in the high (0.5 mg/L) concentration group, evidencing the disorder of nucleotide synthesis and decomposition in <i>B. plicatilis</i>. The biochemical detection of the key enzymes in purine metabolism and pyrimidine metabolism showed the downregulation of Glutamine Synthetase (GS) protein expression and the elevation of Xanthine Oxidase (XOD) activity, which suggested the impaired DNA repair and ROS overproduction. The content of DNA damage biomarker (8-OHdG) increased in treatment groups, and the p53 signaling pathway was found to be activated, as indicated by the elevation of the p53 protein expression and Bax/Bcl-2 ratio. The ROS scavenger (N-acetyl-L-cysteine, NAC) addition effectively alleviated not only ROS overproduction but also DNA damage as well as the activation of apoptosis. The combined results backed up the speculation that purine metabolism and pyrimidine metabolism alteration play a pivotal role in BDE-47-induced ROS overproduction and DNA damage, and the consequent activation of the p53 signaling pathway led to the observed apoptosis in <i>B. plicatilis.</i>https://www.mdpi.com/1422-0067/24/16/12726purine metabolismpyrimidine metabolismreactive oxygen speciesDNA damageapoptosisBDE-47
spellingShingle Sai Cao
Jiayi Wang
Xinye You
Bin Zhou
You Wang
Zhongyuan Zhou
Purine Metabolism and Pyrimidine Metabolism Alteration Is a Potential Mechanism of BDE-47-Induced Apoptosis in Marine Rotifer <i>Brachionus plicatilis</i>
International Journal of Molecular Sciences
purine metabolism
pyrimidine metabolism
reactive oxygen species
DNA damage
apoptosis
BDE-47
title Purine Metabolism and Pyrimidine Metabolism Alteration Is a Potential Mechanism of BDE-47-Induced Apoptosis in Marine Rotifer <i>Brachionus plicatilis</i>
title_full Purine Metabolism and Pyrimidine Metabolism Alteration Is a Potential Mechanism of BDE-47-Induced Apoptosis in Marine Rotifer <i>Brachionus plicatilis</i>
title_fullStr Purine Metabolism and Pyrimidine Metabolism Alteration Is a Potential Mechanism of BDE-47-Induced Apoptosis in Marine Rotifer <i>Brachionus plicatilis</i>
title_full_unstemmed Purine Metabolism and Pyrimidine Metabolism Alteration Is a Potential Mechanism of BDE-47-Induced Apoptosis in Marine Rotifer <i>Brachionus plicatilis</i>
title_short Purine Metabolism and Pyrimidine Metabolism Alteration Is a Potential Mechanism of BDE-47-Induced Apoptosis in Marine Rotifer <i>Brachionus plicatilis</i>
title_sort purine metabolism and pyrimidine metabolism alteration is a potential mechanism of bde 47 induced apoptosis in marine rotifer i brachionus plicatilis i
topic purine metabolism
pyrimidine metabolism
reactive oxygen species
DNA damage
apoptosis
BDE-47
url https://www.mdpi.com/1422-0067/24/16/12726
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