Isothiazolinone dysregulates the pattern of miRNA secretion: Endocrine implications for neurogenesis
Isothiazolinones are extensively used as preservatives and disinfectants in personal care products and household items. The unintended exposure of humans and animals to isothiazolinones has led to increasing concerns about their health hazards. The compound 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-on...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Environment International |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412023005810 |
| _version_ | 1797615968509231104 |
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| author | Lizhu Tang Jing Li Chenyan Hu Bingsheng Zhou Paul K.S. Lam Lianguo Chen |
| author_facet | Lizhu Tang Jing Li Chenyan Hu Bingsheng Zhou Paul K.S. Lam Lianguo Chen |
| author_sort | Lizhu Tang |
| collection | DOAJ |
| description | Isothiazolinones are extensively used as preservatives and disinfectants in personal care products and household items. The unintended exposure of humans and animals to isothiazolinones has led to increasing concerns about their health hazards. The compound 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT), a representative isothiazolinone, can simultaneously induce endocrine disruption and neurotoxicity. However, the underlying mechanisms and linkages remain unclear. Our purpose was to elucidate the role of miRNAs as the signaling communicator during the crosstalk between endocrine and nervous systems in response to DCOIT stress. H295R cells were exposed to DCOIT, after which the alterations in intracellular miRNA composition, exosome secretory machinery, and extracellular miRNA composition were examined. Then, a PC12 cell line of neuronal differentiation potential was cultured with the extract of extracellular miRNAs from DCOIT-exposed H295R cell media to explore the functional implications in neurogenesis. The results showed that DCOIT exposure resulted in 349 differentially expressed miRNAs (DEMs) in H295R cells, which were closely related to the regulation of multiple endocrine pathways. In the media of H295R cells exposed to DCOIT, 66 DEMs were identified, showing distinct compositions compared to intracellular DEMs with only 2 common DEMs (e.g., novel-m0541-5p of inverse changes in the cell and medium). Functional annotation showed that extracellular DEMs were not only associated with sex endocrine synchronization, but were also implicated in nervous system development, morphogenesis, and tumor. Incubating PC12 cells with the extracellular exosomes (containing miRNAs) from DCOIT-exposed H295R cells significantly increased the neurite growth, promoted neuronal differentiation, and shaped the transcriptomic fingerprint, implying that miRNAs may communicate transduction of toxic information of DCOIT in endocrine system to neurons. Overall, the present findings provide novel insight into the endocrine disrupting and neural toxicity of DCOIT. The miRNAs have the potential to serve as the epigenetic mechanism of systems toxicology. |
| first_indexed | 2024-03-11T07:34:33Z |
| format | Article |
| id | doaj.art-06ba26c71a724b5780d6bbdb82a0d52b |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-03-11T07:34:33Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-06ba26c71a724b5780d6bbdb82a0d52b2023-11-17T05:24:56ZengElsevierEnvironment International0160-41202023-11-01181108308Isothiazolinone dysregulates the pattern of miRNA secretion: Endocrine implications for neurogenesisLizhu Tang0Jing Li1Chenyan Hu2Bingsheng Zhou3Paul K.S. Lam4Lianguo Chen5Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaInstitute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaSchool of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430072, ChinaInstitute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaDepartment of Science, School of Science and Technology, Hong Kong Metropolitan University, Kowloon, Hong Kong, ChinaInstitute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; Corresponding author.Isothiazolinones are extensively used as preservatives and disinfectants in personal care products and household items. The unintended exposure of humans and animals to isothiazolinones has led to increasing concerns about their health hazards. The compound 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT), a representative isothiazolinone, can simultaneously induce endocrine disruption and neurotoxicity. However, the underlying mechanisms and linkages remain unclear. Our purpose was to elucidate the role of miRNAs as the signaling communicator during the crosstalk between endocrine and nervous systems in response to DCOIT stress. H295R cells were exposed to DCOIT, after which the alterations in intracellular miRNA composition, exosome secretory machinery, and extracellular miRNA composition were examined. Then, a PC12 cell line of neuronal differentiation potential was cultured with the extract of extracellular miRNAs from DCOIT-exposed H295R cell media to explore the functional implications in neurogenesis. The results showed that DCOIT exposure resulted in 349 differentially expressed miRNAs (DEMs) in H295R cells, which were closely related to the regulation of multiple endocrine pathways. In the media of H295R cells exposed to DCOIT, 66 DEMs were identified, showing distinct compositions compared to intracellular DEMs with only 2 common DEMs (e.g., novel-m0541-5p of inverse changes in the cell and medium). Functional annotation showed that extracellular DEMs were not only associated with sex endocrine synchronization, but were also implicated in nervous system development, morphogenesis, and tumor. Incubating PC12 cells with the extracellular exosomes (containing miRNAs) from DCOIT-exposed H295R cells significantly increased the neurite growth, promoted neuronal differentiation, and shaped the transcriptomic fingerprint, implying that miRNAs may communicate transduction of toxic information of DCOIT in endocrine system to neurons. Overall, the present findings provide novel insight into the endocrine disrupting and neural toxicity of DCOIT. The miRNAs have the potential to serve as the epigenetic mechanism of systems toxicology.http://www.sciencedirect.com/science/article/pii/S0160412023005810IsothiazolinonemiRNAsEndocrine disruptionNeurotoxicityExosome |
| spellingShingle | Lizhu Tang Jing Li Chenyan Hu Bingsheng Zhou Paul K.S. Lam Lianguo Chen Isothiazolinone dysregulates the pattern of miRNA secretion: Endocrine implications for neurogenesis Environment International Isothiazolinone miRNAs Endocrine disruption Neurotoxicity Exosome |
| title | Isothiazolinone dysregulates the pattern of miRNA secretion: Endocrine implications for neurogenesis |
| title_full | Isothiazolinone dysregulates the pattern of miRNA secretion: Endocrine implications for neurogenesis |
| title_fullStr | Isothiazolinone dysregulates the pattern of miRNA secretion: Endocrine implications for neurogenesis |
| title_full_unstemmed | Isothiazolinone dysregulates the pattern of miRNA secretion: Endocrine implications for neurogenesis |
| title_short | Isothiazolinone dysregulates the pattern of miRNA secretion: Endocrine implications for neurogenesis |
| title_sort | isothiazolinone dysregulates the pattern of mirna secretion endocrine implications for neurogenesis |
| topic | Isothiazolinone miRNAs Endocrine disruption Neurotoxicity Exosome |
| url | http://www.sciencedirect.com/science/article/pii/S0160412023005810 |
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