Evolutionarily Ancient Caspase-9 Sensitizes Immune Effector Coelomocytes to Cadmium-Induced Cell Death in the Sea Cucumber, Holothuria leucospilota
Heavy-metal pollution has increasingly jeopardized the habitats of marine organisms including the sea cucumber, a seafloor scavenger vital to seawater bio-decontamination, ocean de-acidification and coral-reef protection. Normal physiology including immune functions of sea cucumbers is toxicological...
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| Formato: | Artigo |
| Idioma: | English |
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Frontiers Media S.A.
2022-07-01
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| Colecção: | Frontiers in Immunology |
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| Acesso em linha: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.927880/full |
| _version_ | 1828779838314381312 |
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| author | Xiaomin Li Xiaomin Li Ting Chen Ting Chen Xiaofen Wu Zhuobo Li Zhuobo Li Xin Zhang Xin Zhang Xiao Jiang Xiao Jiang Peng Luo Peng Luo Chaoqun Hu Chaoqun Hu Nai-Kei Wong Nai-Kei Wong Chunhua Ren Chunhua Ren |
| author_facet | Xiaomin Li Xiaomin Li Ting Chen Ting Chen Xiaofen Wu Zhuobo Li Zhuobo Li Xin Zhang Xin Zhang Xiao Jiang Xiao Jiang Peng Luo Peng Luo Chaoqun Hu Chaoqun Hu Nai-Kei Wong Nai-Kei Wong Chunhua Ren Chunhua Ren |
| author_sort | Xiaomin Li |
| collection | DOAJ |
| description | Heavy-metal pollution has increasingly jeopardized the habitats of marine organisms including the sea cucumber, a seafloor scavenger vital to seawater bio-decontamination, ocean de-acidification and coral-reef protection. Normal physiology including immune functions of sea cucumbers is toxicologically modulated by marine metal pollutants such as cadmium (Cd). The processes underpinning Cd’s toxic effects on immune systems in the sea cucumber, Holothuria leucospilota, are still poorly understood. To this end, we cloned and characterized a full-length caspase-9 (Hl-CASP9) cDNA in the sea cucumber, Holothuria leucospilota. Hl-CASP9 mRNA levels evolved dynamically during embryonic development. Coelomocytes, a type of phagocytic immune effectors central to H. leucospilota immunity, were found to express Hl-CASP9 mRNA most abundantly. Hl-CASP9 protein structurally resembles caspases-2 and -9 in both invertebrate and vertebrate species, comprising a CARD domain and a CASc domain. Remarkably, Hl-CASP9 was transcriptionally sensitive to abiotic oxidative stress inducers including hydrogen peroxide (H2O2), nitric oxide (•NO) and cadmium (Cd), but insensitive to immunostimulants including lipopolysaccharide (LPS), and poly(I:C). Overexpression of Hl-CASP9 augmented mitochondria-dependent apoptosis in HEK293T cells, while knock-down of Hl-CASP9 blunted Cd-induced coelomocyte apoptosis in vivo. Overall, we illustrate that an evolutionarily ancient caspase-9-dependent pathway exists to sensitize coelomocytes to premature cell death precipitated by heavy metal pollutants, with important implications for negative modulation of organismal immune response in marine invertebrates. |
| first_indexed | 2024-12-11T17:08:37Z |
| format | Article |
| id | doaj.art-ecb6f4ac45c84f5cb15ef3c15f2d0885 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T17:08:37Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ecb6f4ac45c84f5cb15ef3c15f2d08852022-12-22T00:57:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.927880927880Evolutionarily Ancient Caspase-9 Sensitizes Immune Effector Coelomocytes to Cadmium-Induced Cell Death in the Sea Cucumber, Holothuria leucospilotaXiaomin Li0Xiaomin Li1Ting Chen2Ting Chen3Xiaofen Wu4Zhuobo Li5Zhuobo Li6Xin Zhang7Xin Zhang8Xiao Jiang9Xiao Jiang10Peng Luo11Peng Luo12Chaoqun Hu13Chaoqun Hu14Nai-Kei Wong15Nai-Kei Wong16Chunhua Ren17Chunhua Ren18CAS Key Laboratory of Tropical Marine Bio-resources and Ecology (LMB), South China Sea Institute of Oceanology, Chinese Academy of Sciences (CAS), Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaCAS Key Laboratory of Tropical Marine Bio-resources and Ecology (LMB), South China Sea Institute of Oceanology, Chinese Academy of Sciences (CAS), Guangzhou, ChinaSouthern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, ChinaInstitute for Integrative Biology of the Cell, University of Paris-Saclay, Paris, FranceCAS Key Laboratory of Tropical Marine Bio-resources and Ecology (LMB), South China Sea Institute of Oceanology, Chinese Academy of Sciences (CAS), Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaCAS Key Laboratory of Tropical Marine Bio-resources and Ecology (LMB), South China Sea Institute of Oceanology, Chinese Academy of Sciences (CAS), Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaCAS Key Laboratory of Tropical Marine Bio-resources and Ecology (LMB), South China Sea Institute of Oceanology, Chinese Academy of Sciences (CAS), Guangzhou, ChinaSouthern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, ChinaCAS Key Laboratory of Tropical Marine Bio-resources and Ecology (LMB), South China Sea Institute of Oceanology, Chinese Academy of Sciences (CAS), Guangzhou, ChinaSouthern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, ChinaCAS Key Laboratory of Tropical Marine Bio-resources and Ecology (LMB), South China Sea Institute of Oceanology, Chinese Academy of Sciences (CAS), Guangzhou, ChinaSouthern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, ChinaClinical Pharmacology Section, Department of Pharmacology, Shantou University of Medical College, Shantou, ChinaGuangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, ChinaCAS Key Laboratory of Tropical Marine Bio-resources and Ecology (LMB), South China Sea Institute of Oceanology, Chinese Academy of Sciences (CAS), Guangzhou, ChinaSouthern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, ChinaHeavy-metal pollution has increasingly jeopardized the habitats of marine organisms including the sea cucumber, a seafloor scavenger vital to seawater bio-decontamination, ocean de-acidification and coral-reef protection. Normal physiology including immune functions of sea cucumbers is toxicologically modulated by marine metal pollutants such as cadmium (Cd). The processes underpinning Cd’s toxic effects on immune systems in the sea cucumber, Holothuria leucospilota, are still poorly understood. To this end, we cloned and characterized a full-length caspase-9 (Hl-CASP9) cDNA in the sea cucumber, Holothuria leucospilota. Hl-CASP9 mRNA levels evolved dynamically during embryonic development. Coelomocytes, a type of phagocytic immune effectors central to H. leucospilota immunity, were found to express Hl-CASP9 mRNA most abundantly. Hl-CASP9 protein structurally resembles caspases-2 and -9 in both invertebrate and vertebrate species, comprising a CARD domain and a CASc domain. Remarkably, Hl-CASP9 was transcriptionally sensitive to abiotic oxidative stress inducers including hydrogen peroxide (H2O2), nitric oxide (•NO) and cadmium (Cd), but insensitive to immunostimulants including lipopolysaccharide (LPS), and poly(I:C). Overexpression of Hl-CASP9 augmented mitochondria-dependent apoptosis in HEK293T cells, while knock-down of Hl-CASP9 blunted Cd-induced coelomocyte apoptosis in vivo. Overall, we illustrate that an evolutionarily ancient caspase-9-dependent pathway exists to sensitize coelomocytes to premature cell death precipitated by heavy metal pollutants, with important implications for negative modulation of organismal immune response in marine invertebrates.https://www.frontiersin.org/articles/10.3389/fimmu.2022.927880/fullcaspase-9cadmiumreactive oxygen/nitrogen species (ROS/RNS)Holothuria leucospilotainvertebrate cell death |
| spellingShingle | Xiaomin Li Xiaomin Li Ting Chen Ting Chen Xiaofen Wu Zhuobo Li Zhuobo Li Xin Zhang Xin Zhang Xiao Jiang Xiao Jiang Peng Luo Peng Luo Chaoqun Hu Chaoqun Hu Nai-Kei Wong Nai-Kei Wong Chunhua Ren Chunhua Ren Evolutionarily Ancient Caspase-9 Sensitizes Immune Effector Coelomocytes to Cadmium-Induced Cell Death in the Sea Cucumber, Holothuria leucospilota Frontiers in Immunology caspase-9 cadmium reactive oxygen/nitrogen species (ROS/RNS) Holothuria leucospilota invertebrate cell death |
| title | Evolutionarily Ancient Caspase-9 Sensitizes Immune Effector Coelomocytes to Cadmium-Induced Cell Death in the Sea Cucumber, Holothuria leucospilota |
| title_full | Evolutionarily Ancient Caspase-9 Sensitizes Immune Effector Coelomocytes to Cadmium-Induced Cell Death in the Sea Cucumber, Holothuria leucospilota |
| title_fullStr | Evolutionarily Ancient Caspase-9 Sensitizes Immune Effector Coelomocytes to Cadmium-Induced Cell Death in the Sea Cucumber, Holothuria leucospilota |
| title_full_unstemmed | Evolutionarily Ancient Caspase-9 Sensitizes Immune Effector Coelomocytes to Cadmium-Induced Cell Death in the Sea Cucumber, Holothuria leucospilota |
| title_short | Evolutionarily Ancient Caspase-9 Sensitizes Immune Effector Coelomocytes to Cadmium-Induced Cell Death in the Sea Cucumber, Holothuria leucospilota |
| title_sort | evolutionarily ancient caspase 9 sensitizes immune effector coelomocytes to cadmium induced cell death in the sea cucumber holothuria leucospilota |
| topic | caspase-9 cadmium reactive oxygen/nitrogen species (ROS/RNS) Holothuria leucospilota invertebrate cell death |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.927880/full |
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