Blockage of KHSRP-NLRP3 by MCC950 Can Reverse the Effect of Manganese-Induced Neuroinflammation in N2a Cells and Rat Brain
Manganese neurotoxicity has been reported to cause a neurodegenerative disease known as parkinsonism. Previous reports have shown that the expression of the KH-type splicing regulatory protein (KHSRP), a nucleic acid-binding protein, and NLRP3 is increased upon Mn exposure. However, the relation bet...
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2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| author | Sharad Singh Ibrahim Ahmed Shaikh Sunil S. More Mater H. Mahnashi Hailah M. Almohaimeed Mohamed El-Sherbiny Mohammed M. Ghoneim Ahmad Umar Harshit Kumar Soni Himanshu Agrawal Basheer Ahmed Mannasaheb Aejaz Abdullatif Khan Uday M. Muddapur S. M. Shakeel Iqubal |
| author_facet | Sharad Singh Ibrahim Ahmed Shaikh Sunil S. More Mater H. Mahnashi Hailah M. Almohaimeed Mohamed El-Sherbiny Mohammed M. Ghoneim Ahmad Umar Harshit Kumar Soni Himanshu Agrawal Basheer Ahmed Mannasaheb Aejaz Abdullatif Khan Uday M. Muddapur S. M. Shakeel Iqubal |
| author_sort | Sharad Singh |
| collection | DOAJ |
| description | Manganese neurotoxicity has been reported to cause a neurodegenerative disease known as parkinsonism. Previous reports have shown that the expression of the KH-type splicing regulatory protein (KHSRP), a nucleic acid-binding protein, and NLRP3 is increased upon Mn exposure. However, the relation between these two during Mn toxicity has not been fully deduced. The mouse neuroblastoma (N2a) and SD rats are treated with LPS and MnCl<sub>2</sub> to evaluate the expression of KHSRP and NLRP3. Further, the effect of the NLRP3 inhibitor MCC950 is checked on the expression of NLRP3, KHSRP and pro-inflammatory markers (TNFα, IL-18 and IL-1β) as well as the caspase-1 enzyme. Our results demonstrated an increment in NLRP3 and KHSRP expression post-MnCl<sub>2</sub> exposure in N2a cells and rat brain, while on the other hand with LPS exposure only NLRP3 expression levels were elevated and KHSRP was found to be unaffected. An increased expression of KHSRP, NLRP3, pro-inflammatory markers and the caspase-1 enzyme was observed to be inhibited with MCC950 treatment in MnCl<sub>2</sub>-exposed cells and rats. Manganese exposure induces NLRP3 and KHSRP expression to induce neuroinflammation, suggesting a correlation between both which functions in toxicity-related pathways. Furthermore, MCC950 treatment reversed the role of KHSRP from anti-inflammatory to pro-inflammatory. |
| first_indexed | 2024-03-09T19:00:52Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:00:52Z |
| publishDate | 2022-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-aca6dc9c562643b8859471c6b99dc39f2023-11-24T05:04:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211322410.3390/ijms232113224Blockage of KHSRP-NLRP3 by MCC950 Can Reverse the Effect of Manganese-Induced Neuroinflammation in N2a Cells and Rat BrainSharad Singh0Ibrahim Ahmed Shaikh1Sunil S. More2Mater H. Mahnashi3Hailah M. Almohaimeed4Mohamed El-Sherbiny5Mohammed M. Ghoneim6Ahmad Umar7Harshit Kumar Soni8Himanshu Agrawal9Basheer Ahmed Mannasaheb10Aejaz Abdullatif Khan11Uday M. Muddapur12S. M. Shakeel Iqubal13School of Basic and Applied Sciences, Dayananda Sagar University, Bangalore 560111, Karnataka, IndiaDepartment of Pharmacology, College of Pharmacy, Najran University, P.O. Box 1988, Najran 66462, Saudi ArabiaSchool of Basic and Applied Sciences, Dayananda Sagar University, Bangalore 560111, Karnataka, IndiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, Najran University, P.O. Box 1988, Najran 66462, Saudi ArabiaDepartment of Basic Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi ArabiaDepartment of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi ArabiaDepartment of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, EgyptDepartment of Chemistry, Faculty of Science and Arts, Najran University, P.O. Box 1988, Najran 11001, Saudi ArabiaDepartment of Zoology, Government Science College, Pandhurna 480334, Madhya Pradesh, IndiaJubilant Biosys Limited (Discovery Biology), Bangalore 560022, Karnataka, IndiaDepartment of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Dariyah, P.O. Box 71666, Riyadh 13713, Saudi ArabiaDepartment of General Science, Ibn Sina National College for Medical Studies, P.O. Box 31906, Jeddah 21418, Saudi ArabiaDepartment of Biotechnology, KLE Technological University, BVB Campus, Hubballi 580031, Karnataka, IndiaDepartment of General Science, Ibn Sina National College for Medical Studies, P.O. Box 31906, Jeddah 21418, Saudi ArabiaManganese neurotoxicity has been reported to cause a neurodegenerative disease known as parkinsonism. Previous reports have shown that the expression of the KH-type splicing regulatory protein (KHSRP), a nucleic acid-binding protein, and NLRP3 is increased upon Mn exposure. However, the relation between these two during Mn toxicity has not been fully deduced. The mouse neuroblastoma (N2a) and SD rats are treated with LPS and MnCl<sub>2</sub> to evaluate the expression of KHSRP and NLRP3. Further, the effect of the NLRP3 inhibitor MCC950 is checked on the expression of NLRP3, KHSRP and pro-inflammatory markers (TNFα, IL-18 and IL-1β) as well as the caspase-1 enzyme. Our results demonstrated an increment in NLRP3 and KHSRP expression post-MnCl<sub>2</sub> exposure in N2a cells and rat brain, while on the other hand with LPS exposure only NLRP3 expression levels were elevated and KHSRP was found to be unaffected. An increased expression of KHSRP, NLRP3, pro-inflammatory markers and the caspase-1 enzyme was observed to be inhibited with MCC950 treatment in MnCl<sub>2</sub>-exposed cells and rats. Manganese exposure induces NLRP3 and KHSRP expression to induce neuroinflammation, suggesting a correlation between both which functions in toxicity-related pathways. Furthermore, MCC950 treatment reversed the role of KHSRP from anti-inflammatory to pro-inflammatory.https://www.mdpi.com/1422-0067/23/21/13224neuroinflammationKHSRPmanganese neurotoxicityN2a cellsParkinson’s |
| spellingShingle | Sharad Singh Ibrahim Ahmed Shaikh Sunil S. More Mater H. Mahnashi Hailah M. Almohaimeed Mohamed El-Sherbiny Mohammed M. Ghoneim Ahmad Umar Harshit Kumar Soni Himanshu Agrawal Basheer Ahmed Mannasaheb Aejaz Abdullatif Khan Uday M. Muddapur S. M. Shakeel Iqubal Blockage of KHSRP-NLRP3 by MCC950 Can Reverse the Effect of Manganese-Induced Neuroinflammation in N2a Cells and Rat Brain International Journal of Molecular Sciences neuroinflammation KHSRP manganese neurotoxicity N2a cells Parkinson’s |
| title | Blockage of KHSRP-NLRP3 by MCC950 Can Reverse the Effect of Manganese-Induced Neuroinflammation in N2a Cells and Rat Brain |
| title_full | Blockage of KHSRP-NLRP3 by MCC950 Can Reverse the Effect of Manganese-Induced Neuroinflammation in N2a Cells and Rat Brain |
| title_fullStr | Blockage of KHSRP-NLRP3 by MCC950 Can Reverse the Effect of Manganese-Induced Neuroinflammation in N2a Cells and Rat Brain |
| title_full_unstemmed | Blockage of KHSRP-NLRP3 by MCC950 Can Reverse the Effect of Manganese-Induced Neuroinflammation in N2a Cells and Rat Brain |
| title_short | Blockage of KHSRP-NLRP3 by MCC950 Can Reverse the Effect of Manganese-Induced Neuroinflammation in N2a Cells and Rat Brain |
| title_sort | blockage of khsrp nlrp3 by mcc950 can reverse the effect of manganese induced neuroinflammation in n2a cells and rat brain |
| topic | neuroinflammation KHSRP manganese neurotoxicity N2a cells Parkinson’s |
| url | https://www.mdpi.com/1422-0067/23/21/13224 |
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