Hypoxia Affects HIF-1/LDH-A Signaling Pathway by Methylation Modification and Transcriptional Regulation in Japanese Flounder (<i>Paralichthys olivaceus</i>)
Japanese flounder (<i>Paralichthys olivaceus</i>) responsive mechanisms to hypoxia are still not fully understood. Therefore, we performed an acute hypoxic treatment (dissolved oxygen at 2.07 ± 0.08 mg/L) on Japanese flounder. It was confirmed that the hypoxic stress affected the physiol...
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MDPI AG
2022-08-01
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| author | Binghua Liu Haishen Wen Jun Yang Xiaohui Li Guangling Li Jingru Zhang Shuxian Wu Ian AE Butts Feng He |
| author_facet | Binghua Liu Haishen Wen Jun Yang Xiaohui Li Guangling Li Jingru Zhang Shuxian Wu Ian AE Butts Feng He |
| author_sort | Binghua Liu |
| collection | DOAJ |
| description | Japanese flounder (<i>Paralichthys olivaceus</i>) responsive mechanisms to hypoxia are still not fully understood. Therefore, we performed an acute hypoxic treatment (dissolved oxygen at 2.07 ± 0.08 mg/L) on Japanese flounder. It was confirmed that the hypoxic stress affected the physiological phenotype through changes in blood physiology (RBC, HGB, WBC), biochemistry (LDH, ALP, ALT, GLU, TC, TG, ALB), and hormone (cortisol) indicators. Hypoxia inducible factor-1 (HIF-1), an essential oxygen homeostasis mediator in organisms consisting of an inducible HIF-1α and a constitutive HIF-1β, and its target gene <i>LDH-A</i> were deeply studied. Results showed that <i>HIF-1α</i> and <i>LDH-A</i> genes were co-expressed and significantly affected by hypoxic stress. The dual-luciferase reporter assay confirmed that transcription factor HIF-1 transcriptionally regulated the <i>LDH-A</i> gene, and its transcription binding sequence was GGACGTGA located at −2343~−2336. The DNA methylation status of <i>HIF-1α</i> and <i>LDH-A</i> genes were detected to understand the mechanism of environmental stress on genes. It was found that hypoxia affected the <i>HIF-1α</i> gene and <i>LDH-A</i> gene methylation levels. The study uncovered HIF-1/LDH-A signaling pathway responsive mechanisms of Japanese flounder to hypoxia in epigenetic modification and transcriptional regulation. Our study is significant to further the understanding of environmental responsive mechanisms as well as providing a reference for aquaculture. |
| first_indexed | 2024-03-09T11:53:01Z |
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| spelling | doaj.art-f92b0880147841b58b945b99cc072ba72023-11-30T23:13:48ZengMDPI AGBiology2079-77372022-08-01118123310.3390/biology11081233Hypoxia Affects HIF-1/LDH-A Signaling Pathway by Methylation Modification and Transcriptional Regulation in Japanese Flounder (<i>Paralichthys olivaceus</i>)Binghua Liu0Haishen Wen1Jun Yang2Xiaohui Li3Guangling Li4Jingru Zhang5Shuxian Wu6Ian AE Butts7Feng He8Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266000, ChinaKey Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266000, ChinaKey Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266000, ChinaKey Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266000, ChinaKey Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266000, ChinaKey Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266000, ChinaKey Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266000, ChinaSchool of Fisheries, Aquaculture and Aquatic Sciences, Auburn University, Auburn, AL 36849, USAKey Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao 266000, ChinaJapanese flounder (<i>Paralichthys olivaceus</i>) responsive mechanisms to hypoxia are still not fully understood. Therefore, we performed an acute hypoxic treatment (dissolved oxygen at 2.07 ± 0.08 mg/L) on Japanese flounder. It was confirmed that the hypoxic stress affected the physiological phenotype through changes in blood physiology (RBC, HGB, WBC), biochemistry (LDH, ALP, ALT, GLU, TC, TG, ALB), and hormone (cortisol) indicators. Hypoxia inducible factor-1 (HIF-1), an essential oxygen homeostasis mediator in organisms consisting of an inducible HIF-1α and a constitutive HIF-1β, and its target gene <i>LDH-A</i> were deeply studied. Results showed that <i>HIF-1α</i> and <i>LDH-A</i> genes were co-expressed and significantly affected by hypoxic stress. The dual-luciferase reporter assay confirmed that transcription factor HIF-1 transcriptionally regulated the <i>LDH-A</i> gene, and its transcription binding sequence was GGACGTGA located at −2343~−2336. The DNA methylation status of <i>HIF-1α</i> and <i>LDH-A</i> genes were detected to understand the mechanism of environmental stress on genes. It was found that hypoxia affected the <i>HIF-1α</i> gene and <i>LDH-A</i> gene methylation levels. The study uncovered HIF-1/LDH-A signaling pathway responsive mechanisms of Japanese flounder to hypoxia in epigenetic modification and transcriptional regulation. Our study is significant to further the understanding of environmental responsive mechanisms as well as providing a reference for aquaculture.https://www.mdpi.com/2079-7737/11/8/1233hypoxia stressJapanese flounderphysiological responsetranscriptional regulationepigenetic modification |
| spellingShingle | Binghua Liu Haishen Wen Jun Yang Xiaohui Li Guangling Li Jingru Zhang Shuxian Wu Ian AE Butts Feng He Hypoxia Affects HIF-1/LDH-A Signaling Pathway by Methylation Modification and Transcriptional Regulation in Japanese Flounder (<i>Paralichthys olivaceus</i>) Biology hypoxia stress Japanese flounder physiological response transcriptional regulation epigenetic modification |
| title | Hypoxia Affects HIF-1/LDH-A Signaling Pathway by Methylation Modification and Transcriptional Regulation in Japanese Flounder (<i>Paralichthys olivaceus</i>) |
| title_full | Hypoxia Affects HIF-1/LDH-A Signaling Pathway by Methylation Modification and Transcriptional Regulation in Japanese Flounder (<i>Paralichthys olivaceus</i>) |
| title_fullStr | Hypoxia Affects HIF-1/LDH-A Signaling Pathway by Methylation Modification and Transcriptional Regulation in Japanese Flounder (<i>Paralichthys olivaceus</i>) |
| title_full_unstemmed | Hypoxia Affects HIF-1/LDH-A Signaling Pathway by Methylation Modification and Transcriptional Regulation in Japanese Flounder (<i>Paralichthys olivaceus</i>) |
| title_short | Hypoxia Affects HIF-1/LDH-A Signaling Pathway by Methylation Modification and Transcriptional Regulation in Japanese Flounder (<i>Paralichthys olivaceus</i>) |
| title_sort | hypoxia affects hif 1 ldh a signaling pathway by methylation modification and transcriptional regulation in japanese flounder i paralichthys olivaceus i |
| topic | hypoxia stress Japanese flounder physiological response transcriptional regulation epigenetic modification |
| url | https://www.mdpi.com/2079-7737/11/8/1233 |
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