Glutathione Peroxidase 4 in Blunt Snout Bream (<i>Megalobrama amblycephala</i>) Regulates Ferroptosis and Inflammation in Response to <i>Aeromonas hydrophila</i> Infection

Glutathione peroxidase 4 (GPX4) plays a crucial role in regulating lipid peroxidation and is associated with infection and inflammation, particularly in terms of its effects on inflammatory cytokines and ferroptosis. This study aimed to investigate the regulatory effects of Gpx4 on the inflammatory...

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Main Authors: Miao He, Huanling Wang, Hong Liu
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Current Issues in Molecular Biology
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Online Access:https://www.mdpi.com/1467-3045/47/5/326
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author Miao He
Huanling Wang
Hong Liu
author_facet Miao He
Huanling Wang
Hong Liu
author_sort Miao He
collection DOAJ
description Glutathione peroxidase 4 (GPX4) plays a crucial role in regulating lipid peroxidation and is associated with infection and inflammation, particularly in terms of its effects on inflammatory cytokines and ferroptosis. This study aimed to investigate the regulatory effects of Gpx4 on the inflammatory response and ferroptosis in blunt snout bream (<i>Megalobrama amblycephala</i>), a significant freshwater fish species in China, after <i>Aeromonas hydrophila</i> infection. Using a bioinformatics analysis, we discovered that Gpx4 has a conserved protein structure and high amino acid identity in various carp species, indicating functional conservation across species and through involution. RT-qPCR analysis revealed that <i>gpx4</i> mRNA increased after the neuroembryonic stage during early development and was particularly highly expressed in the liver of healthy adult fish. Upon <i>A. hydrophila</i> infection, <i>gpx4</i> expression decreased significantly and rapidly in the liver. In L8824 cells, overexpression of <i>gpx4</i> suppressed inflammatory cytokines and inhibited ferroptosis in response to both <i>A. hydrophila</i> infection and induction of ferroptosis-inducer RSL3. These findings highlight the regulatory role of Gpx4 in cellular ferroptosis and inflammation, providing insights into the complex mechanisms of disease resistance and potentially aiding in the development of strategies for disease control in fish.
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spelling doaj-art-513a159752414d5d9599131b71befdfa2025-08-20T02:33:44ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-05-0147532610.3390/cimb47050326Glutathione Peroxidase 4 in Blunt Snout Bream (<i>Megalobrama amblycephala</i>) Regulates Ferroptosis and Inflammation in Response to <i>Aeromonas hydrophila</i> InfectionMiao He0Huanling Wang1Hong Liu2Key Lab of Freshwater Animal Breeding, Ministry of Agriculture and Rural Affair/Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, ChinaKey Lab of Freshwater Animal Breeding, Ministry of Agriculture and Rural Affair/Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, ChinaKey Lab of Freshwater Animal Breeding, Ministry of Agriculture and Rural Affair/Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Fisheries, Huazhong Agricultural University, Wuhan 430070, ChinaGlutathione peroxidase 4 (GPX4) plays a crucial role in regulating lipid peroxidation and is associated with infection and inflammation, particularly in terms of its effects on inflammatory cytokines and ferroptosis. This study aimed to investigate the regulatory effects of Gpx4 on the inflammatory response and ferroptosis in blunt snout bream (<i>Megalobrama amblycephala</i>), a significant freshwater fish species in China, after <i>Aeromonas hydrophila</i> infection. Using a bioinformatics analysis, we discovered that Gpx4 has a conserved protein structure and high amino acid identity in various carp species, indicating functional conservation across species and through involution. RT-qPCR analysis revealed that <i>gpx4</i> mRNA increased after the neuroembryonic stage during early development and was particularly highly expressed in the liver of healthy adult fish. Upon <i>A. hydrophila</i> infection, <i>gpx4</i> expression decreased significantly and rapidly in the liver. In L8824 cells, overexpression of <i>gpx4</i> suppressed inflammatory cytokines and inhibited ferroptosis in response to both <i>A. hydrophila</i> infection and induction of ferroptosis-inducer RSL3. These findings highlight the regulatory role of Gpx4 in cellular ferroptosis and inflammation, providing insights into the complex mechanisms of disease resistance and potentially aiding in the development of strategies for disease control in fish.https://www.mdpi.com/1467-3045/47/5/326<i>Megalobrama amblycephala</i><i>Aeromonas hydrophila</i><i>gpx4</i>ferroptosisinflammation
spellingShingle Miao He
Huanling Wang
Hong Liu
Glutathione Peroxidase 4 in Blunt Snout Bream (<i>Megalobrama amblycephala</i>) Regulates Ferroptosis and Inflammation in Response to <i>Aeromonas hydrophila</i> Infection
Current Issues in Molecular Biology
<i>Megalobrama amblycephala</i>
<i>Aeromonas hydrophila</i>
<i>gpx4</i>
ferroptosis
inflammation
title Glutathione Peroxidase 4 in Blunt Snout Bream (<i>Megalobrama amblycephala</i>) Regulates Ferroptosis and Inflammation in Response to <i>Aeromonas hydrophila</i> Infection
title_full Glutathione Peroxidase 4 in Blunt Snout Bream (<i>Megalobrama amblycephala</i>) Regulates Ferroptosis and Inflammation in Response to <i>Aeromonas hydrophila</i> Infection
title_fullStr Glutathione Peroxidase 4 in Blunt Snout Bream (<i>Megalobrama amblycephala</i>) Regulates Ferroptosis and Inflammation in Response to <i>Aeromonas hydrophila</i> Infection
title_full_unstemmed Glutathione Peroxidase 4 in Blunt Snout Bream (<i>Megalobrama amblycephala</i>) Regulates Ferroptosis and Inflammation in Response to <i>Aeromonas hydrophila</i> Infection
title_short Glutathione Peroxidase 4 in Blunt Snout Bream (<i>Megalobrama amblycephala</i>) Regulates Ferroptosis and Inflammation in Response to <i>Aeromonas hydrophila</i> Infection
title_sort glutathione peroxidase 4 in blunt snout bream i megalobrama amblycephala i regulates ferroptosis and inflammation in response to i aeromonas hydrophila i infection
topic <i>Megalobrama amblycephala</i>
<i>Aeromonas hydrophila</i>
<i>gpx4</i>
ferroptosis
inflammation
url https://www.mdpi.com/1467-3045/47/5/326
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AT huanlingwang glutathioneperoxidase4inbluntsnoutbreamimegalobramaamblycephalairegulatesferroptosisandinflammationinresponsetoiaeromonashydrophilaiinfection
AT hongliu glutathioneperoxidase4inbluntsnoutbreamimegalobramaamblycephalairegulatesferroptosisandinflammationinresponsetoiaeromonashydrophilaiinfection