Triclosan-induced neuroinflammation develops caspase-independent and TNF-α signaling pathway associated necroptosis in Neuro-2a cells
Triclosan (TCS) is widely used in cosmetics and healthcare industry as a broad-spectrum antibacterial agent. The lipophilic property and persistent nature of TCS has led to severe health issues. In the present study, we have evaluated the neuroinflammatory effect of TCS on mouse Neuro-2a cells. Init...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Current Research in Toxicology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666027X22000093 |
| _version_ | 1797978703924297728 |
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| author | Parul Katiyar Somesh Banerjee Sandip Nathani Partha Roy |
| author_facet | Parul Katiyar Somesh Banerjee Sandip Nathani Partha Roy |
| author_sort | Parul Katiyar |
| collection | DOAJ |
| description | Triclosan (TCS) is widely used in cosmetics and healthcare industry as a broad-spectrum antibacterial agent. The lipophilic property and persistent nature of TCS has led to severe health issues. In the present study, we have evaluated the neuroinflammatory effect of TCS on mouse Neuro-2a cells. Initial investigation confirmed a dose-dependent loss in viability and morphology of cells in presence of TCS. The transcription and translation studies confirmed a downregulation in the expression of autophagy markers in Neuro-2a cells. The confocal microscopy study revealed that the abrogated autophagy in TCS-treated cells occurred due to loss in the autophagy flux and prevention in the lipidation of autophagosome bilayer. The fluorescence microscopy also confirmed a loss in the formation of autophagolysosomes in neuronal cells with increasing TCS concentrations. TCS treatment resulted in loss of mitochondrial integrity in cells as evidenced by a decrease in mitochondrial membrane potential in JC-1 staining. Further, the transcriptional and translational studies confirmed the activation of TNF-α signaling pathway in TCS-treated cells thus enhancing the expression of RIPK1, RIPK3 and MLKL proteins and their phosphorylated forms. TCS was also found to increase the tau protein pathogenesis in Neuro-2a cells, which alludes to the development of tau-associated neurodegeneration. Altogether, this study confirms the neuroinflammatory actions of TCS in Neuro-2a cells involving a TNF-α-induced MLKL-mediated signaling. |
| first_indexed | 2024-04-11T05:28:19Z |
| format | Article |
| id | doaj.art-84e7bce1759249978ab1aa190b5c3dfb |
| institution | Directory Open Access Journal |
| issn | 2666-027X |
| language | English |
| last_indexed | 2024-04-11T05:28:19Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Toxicology |
| spelling | doaj.art-84e7bce1759249978ab1aa190b5c3dfb2022-12-23T04:42:15ZengElsevierCurrent Research in Toxicology2666-027X2022-01-013100072Triclosan-induced neuroinflammation develops caspase-independent and TNF-α signaling pathway associated necroptosis in Neuro-2a cellsParul Katiyar0Somesh Banerjee1Sandip Nathani2Partha Roy3Molecular Endocrinology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, IndiaMolecular Endocrinology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, IndiaMolecular Endocrinology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, IndiaCorresponding author.; Molecular Endocrinology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, IndiaTriclosan (TCS) is widely used in cosmetics and healthcare industry as a broad-spectrum antibacterial agent. The lipophilic property and persistent nature of TCS has led to severe health issues. In the present study, we have evaluated the neuroinflammatory effect of TCS on mouse Neuro-2a cells. Initial investigation confirmed a dose-dependent loss in viability and morphology of cells in presence of TCS. The transcription and translation studies confirmed a downregulation in the expression of autophagy markers in Neuro-2a cells. The confocal microscopy study revealed that the abrogated autophagy in TCS-treated cells occurred due to loss in the autophagy flux and prevention in the lipidation of autophagosome bilayer. The fluorescence microscopy also confirmed a loss in the formation of autophagolysosomes in neuronal cells with increasing TCS concentrations. TCS treatment resulted in loss of mitochondrial integrity in cells as evidenced by a decrease in mitochondrial membrane potential in JC-1 staining. Further, the transcriptional and translational studies confirmed the activation of TNF-α signaling pathway in TCS-treated cells thus enhancing the expression of RIPK1, RIPK3 and MLKL proteins and their phosphorylated forms. TCS was also found to increase the tau protein pathogenesis in Neuro-2a cells, which alludes to the development of tau-associated neurodegeneration. Altogether, this study confirms the neuroinflammatory actions of TCS in Neuro-2a cells involving a TNF-α-induced MLKL-mediated signaling.http://www.sciencedirect.com/science/article/pii/S2666027X22000093TriclosanNeuro-2aAutophagyNecroptosisTau pathogenesis |
| spellingShingle | Parul Katiyar Somesh Banerjee Sandip Nathani Partha Roy Triclosan-induced neuroinflammation develops caspase-independent and TNF-α signaling pathway associated necroptosis in Neuro-2a cells Current Research in Toxicology Triclosan Neuro-2a Autophagy Necroptosis Tau pathogenesis |
| title | Triclosan-induced neuroinflammation develops caspase-independent and TNF-α signaling pathway associated necroptosis in Neuro-2a cells |
| title_full | Triclosan-induced neuroinflammation develops caspase-independent and TNF-α signaling pathway associated necroptosis in Neuro-2a cells |
| title_fullStr | Triclosan-induced neuroinflammation develops caspase-independent and TNF-α signaling pathway associated necroptosis in Neuro-2a cells |
| title_full_unstemmed | Triclosan-induced neuroinflammation develops caspase-independent and TNF-α signaling pathway associated necroptosis in Neuro-2a cells |
| title_short | Triclosan-induced neuroinflammation develops caspase-independent and TNF-α signaling pathway associated necroptosis in Neuro-2a cells |
| title_sort | triclosan induced neuroinflammation develops caspase independent and tnf α signaling pathway associated necroptosis in neuro 2a cells |
| topic | Triclosan Neuro-2a Autophagy Necroptosis Tau pathogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S2666027X22000093 |
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