Carnosine Synthase (<i>Ts</i>ATPGD) Alleviates Lipid Peroxidation Under Transcriptional Control by an <i>Nfe2</i>-like Gene in <i>Tridacna Squamosa</i>

As an important mollusk in reef ecosystems, <i>Tridacna squamosa</i> forms pro-survival symbiotic relationships that hinge on an exquisite redox equilibrium between the host and the photosynthetic symbiont, zooxanthellae. The exact regulatory mechanisms thereof remain poorly understood....

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Main Authors: Zhuo Yang, Nai-Kei Wong, Fan Mao, Siwei Wu, Wenjie Yi, Ziniu Yu, Yang Zhang
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/13/11/1351
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author Zhuo Yang
Nai-Kei Wong
Fan Mao
Siwei Wu
Wenjie Yi
Ziniu Yu
Yang Zhang
author_facet Zhuo Yang
Nai-Kei Wong
Fan Mao
Siwei Wu
Wenjie Yi
Ziniu Yu
Yang Zhang
author_sort Zhuo Yang
collection DOAJ
description As an important mollusk in reef ecosystems, <i>Tridacna squamosa</i> forms pro-survival symbiotic relationships that hinge on an exquisite redox equilibrium between the host and the photosynthetic symbiont, zooxanthellae. The exact regulatory mechanisms thereof remain poorly understood. In this study, a novel Nfe2-like transcription factor in <i>T. squamosa</i> was identified and characterized with respect to its antioxidant and cytoprotective roles. Gene structure and phylogenetic analysis reveal that <i>T. squamosa</i> possesses a single transcription factor <i>Ts</i>Nfe2l in contrast to mammalian Nfe2l1 (Nrf1) and Nfe2l2 (Nrf2), belonging to protein members of the bZIP-NFE2 subfamily and functionally resembling the mammalian Nfe2l1. A conserved bZIP domain permits its binding to the antioxidant response element (ARE) in vitro and in HEK293T cells. Further analyses such as promoter prediction suggest that <i>Ts</i>Nfe2l target genes engage mainly in the regulation of multiple enzymes involved in antioxidation and allied pathways. Notably, <i>Ts</i>Nfe2l transcriptionally upregulates carnosine synthase (<i>Ts</i>ATPGD), which subsequently produces <i>L</i>-carnosine abundantly to shield cells from oxidative damage. Moreover, the blockage of <i>Ts</i>Nfe2l nucleic acid binding reduced the expression of <i>Ts</i>ATPGD and <i>L</i>-carnosine content in the gill, resulting in elevated lipid peroxidation. Collectively, our findings establish novel molecular insight into <i>Ts</i>Nfe2l as a critical regulator of redox homeostasis in <i>T. squamosa</i> through carnosine synthesis.
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spelling doaj-art-d9ac9241a8e4499395caaf85b65916632024-11-26T17:47:05ZengMDPI AGAntioxidants2076-39212024-11-011311135110.3390/antiox13111351Carnosine Synthase (<i>Ts</i>ATPGD) Alleviates Lipid Peroxidation Under Transcriptional Control by an <i>Nfe2</i>-like Gene in <i>Tridacna Squamosa</i>Zhuo Yang0Nai-Kei Wong1Fan Mao2Siwei Wu3Wenjie Yi4Ziniu Yu5Yang Zhang6Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Key Laboratory of Tropical Marine Bio-Resources and Ecology and Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, ChinaDepartment of Pharmacology, Shantou University Medical College, Shantou 515041, ChinaKey Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Key Laboratory of Tropical Marine Bio-Resources and Ecology and Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, ChinaKey Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Key Laboratory of Tropical Marine Bio-Resources and Ecology and Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, ChinaKey Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Key Laboratory of Tropical Marine Bio-Resources and Ecology and Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, ChinaKey Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Key Laboratory of Tropical Marine Bio-Resources and Ecology and Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, ChinaKey Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Key Laboratory of Tropical Marine Bio-Resources and Ecology and Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, ChinaAs an important mollusk in reef ecosystems, <i>Tridacna squamosa</i> forms pro-survival symbiotic relationships that hinge on an exquisite redox equilibrium between the host and the photosynthetic symbiont, zooxanthellae. The exact regulatory mechanisms thereof remain poorly understood. In this study, a novel Nfe2-like transcription factor in <i>T. squamosa</i> was identified and characterized with respect to its antioxidant and cytoprotective roles. Gene structure and phylogenetic analysis reveal that <i>T. squamosa</i> possesses a single transcription factor <i>Ts</i>Nfe2l in contrast to mammalian Nfe2l1 (Nrf1) and Nfe2l2 (Nrf2), belonging to protein members of the bZIP-NFE2 subfamily and functionally resembling the mammalian Nfe2l1. A conserved bZIP domain permits its binding to the antioxidant response element (ARE) in vitro and in HEK293T cells. Further analyses such as promoter prediction suggest that <i>Ts</i>Nfe2l target genes engage mainly in the regulation of multiple enzymes involved in antioxidation and allied pathways. Notably, <i>Ts</i>Nfe2l transcriptionally upregulates carnosine synthase (<i>Ts</i>ATPGD), which subsequently produces <i>L</i>-carnosine abundantly to shield cells from oxidative damage. Moreover, the blockage of <i>Ts</i>Nfe2l nucleic acid binding reduced the expression of <i>Ts</i>ATPGD and <i>L</i>-carnosine content in the gill, resulting in elevated lipid peroxidation. Collectively, our findings establish novel molecular insight into <i>Ts</i>Nfe2l as a critical regulator of redox homeostasis in <i>T. squamosa</i> through carnosine synthesis.https://www.mdpi.com/2076-3921/13/11/1351<i>Tridacna squamosa</i>Nfe2l genecarnosine synthase (ATPGD)lipid peroxidation<i>L</i>-carnosine
spellingShingle Zhuo Yang
Nai-Kei Wong
Fan Mao
Siwei Wu
Wenjie Yi
Ziniu Yu
Yang Zhang
Carnosine Synthase (<i>Ts</i>ATPGD) Alleviates Lipid Peroxidation Under Transcriptional Control by an <i>Nfe2</i>-like Gene in <i>Tridacna Squamosa</i>
Antioxidants
<i>Tridacna squamosa</i>
Nfe2l gene
carnosine synthase (ATPGD)
lipid peroxidation
<i>L</i>-carnosine
title Carnosine Synthase (<i>Ts</i>ATPGD) Alleviates Lipid Peroxidation Under Transcriptional Control by an <i>Nfe2</i>-like Gene in <i>Tridacna Squamosa</i>
title_full Carnosine Synthase (<i>Ts</i>ATPGD) Alleviates Lipid Peroxidation Under Transcriptional Control by an <i>Nfe2</i>-like Gene in <i>Tridacna Squamosa</i>
title_fullStr Carnosine Synthase (<i>Ts</i>ATPGD) Alleviates Lipid Peroxidation Under Transcriptional Control by an <i>Nfe2</i>-like Gene in <i>Tridacna Squamosa</i>
title_full_unstemmed Carnosine Synthase (<i>Ts</i>ATPGD) Alleviates Lipid Peroxidation Under Transcriptional Control by an <i>Nfe2</i>-like Gene in <i>Tridacna Squamosa</i>
title_short Carnosine Synthase (<i>Ts</i>ATPGD) Alleviates Lipid Peroxidation Under Transcriptional Control by an <i>Nfe2</i>-like Gene in <i>Tridacna Squamosa</i>
title_sort carnosine synthase i ts i atpgd alleviates lipid peroxidation under transcriptional control by an i nfe2 i like gene in i tridacna squamosa i
topic <i>Tridacna squamosa</i>
Nfe2l gene
carnosine synthase (ATPGD)
lipid peroxidation
<i>L</i>-carnosine
url https://www.mdpi.com/2076-3921/13/11/1351
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