Characterization of Biological Pathways Regulating Acute Cold Resistance of Zebrafish
Low temperature stress represents a major threat to the lives of both farmed and wild fish species. However, biological pathways determining the development of cold resistance in fish remain largely unknown. Zebrafish larvae at 96 hpf were exposed to lethal cold stress (10 °C) for different time per...
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/6/3028 |
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| author | Jing Ren Yong Long Ran Liu Guili Song Qing Li Zongbin Cui |
| author_facet | Jing Ren Yong Long Ran Liu Guili Song Qing Li Zongbin Cui |
| author_sort | Jing Ren |
| collection | DOAJ |
| description | Low temperature stress represents a major threat to the lives of both farmed and wild fish species. However, biological pathways determining the development of cold resistance in fish remain largely unknown. Zebrafish larvae at 96 hpf were exposed to lethal cold stress (10 °C) for different time periods to evaluate the adverse effects at organism, tissue and cell levels. Time series RNA sequencing (RNA-seq) experiments were performed to delineate the transcriptomic landscape of zebrafish larvae under cold stress and during the subsequent rewarming phase. The genes regulated by cold stress were characterized by progressively enhanced or decreased expression, whereas the genes associated with rewarming were characterized by rapid upregulation upon return to normal temperature (28 °C). Genes such as <i>trib3</i>, <i>dusp5</i> and <i>otud1</i> were identified as the representative molecular markers of cold-induced damages through network analysis. Biological pathways involved in cold stress responses were mined from the transcriptomic data and their functions in regulating cold resistance were validated using specific inhibitors. The autophagy, FoxO and MAPK (mitogen-activated protein kinase) signaling pathways were revealed to be survival pathways for enhancing cold resistance, while apoptosis and necroptosis were the death pathways responsible for cold-induced mortality. Functional mechanisms of the survival-enhancing factors Foxo1, ERK (extracellular signal-regulated kinase) and p38 MAPK were further characterized by inhibiting their activities upon cold stress and analyzing gene expression though RNA-seq. These factors were demonstrated to determine the cold resistance of zebrafish through regulating apoptosis and p53 signaling pathway. These findings have provided novel insights into the stress responses elicited by lethal cold and shed new light on the molecular mechanisms underlying cold resistance of fish. |
| first_indexed | 2024-03-10T13:11:20Z |
| format | Article |
| id | doaj.art-229b1caf6ef942778fd1d6c0a6028ffa |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:11:20Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-229b1caf6ef942778fd1d6c0a6028ffa2023-11-21T10:44:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01226302810.3390/ijms22063028Characterization of Biological Pathways Regulating Acute Cold Resistance of ZebrafishJing Ren0Yong Long1Ran Liu2Guili Song3Qing Li4Zongbin Cui5State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaLow temperature stress represents a major threat to the lives of both farmed and wild fish species. However, biological pathways determining the development of cold resistance in fish remain largely unknown. Zebrafish larvae at 96 hpf were exposed to lethal cold stress (10 °C) for different time periods to evaluate the adverse effects at organism, tissue and cell levels. Time series RNA sequencing (RNA-seq) experiments were performed to delineate the transcriptomic landscape of zebrafish larvae under cold stress and during the subsequent rewarming phase. The genes regulated by cold stress were characterized by progressively enhanced or decreased expression, whereas the genes associated with rewarming were characterized by rapid upregulation upon return to normal temperature (28 °C). Genes such as <i>trib3</i>, <i>dusp5</i> and <i>otud1</i> were identified as the representative molecular markers of cold-induced damages through network analysis. Biological pathways involved in cold stress responses were mined from the transcriptomic data and their functions in regulating cold resistance were validated using specific inhibitors. The autophagy, FoxO and MAPK (mitogen-activated protein kinase) signaling pathways were revealed to be survival pathways for enhancing cold resistance, while apoptosis and necroptosis were the death pathways responsible for cold-induced mortality. Functional mechanisms of the survival-enhancing factors Foxo1, ERK (extracellular signal-regulated kinase) and p38 MAPK were further characterized by inhibiting their activities upon cold stress and analyzing gene expression though RNA-seq. These factors were demonstrated to determine the cold resistance of zebrafish through regulating apoptosis and p53 signaling pathway. These findings have provided novel insights into the stress responses elicited by lethal cold and shed new light on the molecular mechanisms underlying cold resistance of fish.https://www.mdpi.com/1422-0067/22/6/3028cold resistancezebrafishstress responsebiological pathwaystranscriptional regulationcell death |
| spellingShingle | Jing Ren Yong Long Ran Liu Guili Song Qing Li Zongbin Cui Characterization of Biological Pathways Regulating Acute Cold Resistance of Zebrafish International Journal of Molecular Sciences cold resistance zebrafish stress response biological pathways transcriptional regulation cell death |
| title | Characterization of Biological Pathways Regulating Acute Cold Resistance of Zebrafish |
| title_full | Characterization of Biological Pathways Regulating Acute Cold Resistance of Zebrafish |
| title_fullStr | Characterization of Biological Pathways Regulating Acute Cold Resistance of Zebrafish |
| title_full_unstemmed | Characterization of Biological Pathways Regulating Acute Cold Resistance of Zebrafish |
| title_short | Characterization of Biological Pathways Regulating Acute Cold Resistance of Zebrafish |
| title_sort | characterization of biological pathways regulating acute cold resistance of zebrafish |
| topic | cold resistance zebrafish stress response biological pathways transcriptional regulation cell death |
| url | https://www.mdpi.com/1422-0067/22/6/3028 |
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