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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Bibliographic Details
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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Summary: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.
ISSN:2076-3921