Peroxisomal ether-glycerophospholipid synthesis is dysregulated after TBI
Ether-glycerophospholipids (ether-GPs), the ether bond- (– O –) containing glycerophospholipids, are major components of the brain lipidome. Ether-GPs play a crucial role in regulating neuronal function, and their deficiency has been implicated in many neurodegenerative diseases. However, how they a...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227525000811 |
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| author | Amir A. Mehrabani-Tabari Nivedita Hegdekar Sabrina Bustos Yulemni Morel Yuanyuan Ji Sazia Arefin Kachi Olivia Pettyjohn-Robin Sagarina Thapa Maya Bhattiprolu Marta M. Lipinski Jace W. Jones Chinmoy Sarkar |
| author_facet | Amir A. Mehrabani-Tabari Nivedita Hegdekar Sabrina Bustos Yulemni Morel Yuanyuan Ji Sazia Arefin Kachi Olivia Pettyjohn-Robin Sagarina Thapa Maya Bhattiprolu Marta M. Lipinski Jace W. Jones Chinmoy Sarkar |
| author_sort | Amir A. Mehrabani-Tabari |
| collection | DOAJ |
| description | Ether-glycerophospholipids (ether-GPs), the ether bond- (– O –) containing glycerophospholipids, are major components of the brain lipidome. Ether-GPs play a crucial role in regulating neuronal function, and their deficiency has been implicated in many neurodegenerative diseases. However, how they are affected after traumatic brain injury (TBI) is not known. Our data demonstrate a significant decrease in ether-GPs abundance in the mouse cortex following controlled cortical impact (CCI)-induced TBI. This is at least in part due to the impairment of peroxisomal ether-GP synthesis in the mouse brain after TBI. We detected dysregulation of peroxisomal ether-GPs synthesizing enzymes – glyceronephosphate-O-acyltransferase (GNPAT) and alkylglycerone phosphate synthase (AGPS) in the injured mouse brains. Our data demonstrate a significant decline in GNPAT level in the peroxisomal fraction and a marked accumulation of AGPS in the cytosol of mouse cortices after TBI. To restore the ether-GP level in the injured brain, we treated TBI mice with an ether-GP precursor, 1-O-octadecylglycerol (OAG), to bypass the peroxisomal ether-GPs synthesizing steps. OAG partially restored the levels of several ether-GPs, attenuated inflammatory cytokine expression, and improved their functional recovery after TBI. Taken together, our data demonstrate that the decline in ether-GPs abundance after TBI is at least in part due to the impairment in peroxisomal ether-GPs synthesis and that restoration of ether-GPs by OAG treatment can improve TBI outcomes. |
| format | Article |
| id | doaj-art-9716a4d9fcab4334a281e0810344f6a4 |
| institution | Kabale University |
| issn | 0022-2275 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj-art-9716a4d9fcab4334a281e0810344f6a42025-08-20T03:30:32ZengElsevierJournal of Lipid Research0022-22752025-06-0166610082110.1016/j.jlr.2025.100821Peroxisomal ether-glycerophospholipid synthesis is dysregulated after TBIAmir A. Mehrabani-Tabari0Nivedita Hegdekar1Sabrina Bustos2Yulemni Morel3Yuanyuan Ji4Sazia Arefin Kachi5Olivia Pettyjohn-Robin6Sagarina Thapa7Maya Bhattiprolu8Marta M. Lipinski9Jace W. Jones10Chinmoy Sarkar11Shock, Trauma and Anesthesiology Research (STAR) Center, Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USAShock, Trauma and Anesthesiology Research (STAR) Center, Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USAShock, Trauma and Anesthesiology Research (STAR) Center, Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USADepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USADepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USADepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USAShock, Trauma and Anesthesiology Research (STAR) Center, Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USAShock, Trauma and Anesthesiology Research (STAR) Center, Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USADepartment of Biology, University of Maryland, College Park, MD, USAShock, Trauma and Anesthesiology Research (STAR) Center, Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USADepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USAShock, Trauma and Anesthesiology Research (STAR) Center, Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, USA; For correspondence: Chinmoy SarkarEther-glycerophospholipids (ether-GPs), the ether bond- (– O –) containing glycerophospholipids, are major components of the brain lipidome. Ether-GPs play a crucial role in regulating neuronal function, and their deficiency has been implicated in many neurodegenerative diseases. However, how they are affected after traumatic brain injury (TBI) is not known. Our data demonstrate a significant decrease in ether-GPs abundance in the mouse cortex following controlled cortical impact (CCI)-induced TBI. This is at least in part due to the impairment of peroxisomal ether-GP synthesis in the mouse brain after TBI. We detected dysregulation of peroxisomal ether-GPs synthesizing enzymes – glyceronephosphate-O-acyltransferase (GNPAT) and alkylglycerone phosphate synthase (AGPS) in the injured mouse brains. Our data demonstrate a significant decline in GNPAT level in the peroxisomal fraction and a marked accumulation of AGPS in the cytosol of mouse cortices after TBI. To restore the ether-GP level in the injured brain, we treated TBI mice with an ether-GP precursor, 1-O-octadecylglycerol (OAG), to bypass the peroxisomal ether-GPs synthesizing steps. OAG partially restored the levels of several ether-GPs, attenuated inflammatory cytokine expression, and improved their functional recovery after TBI. Taken together, our data demonstrate that the decline in ether-GPs abundance after TBI is at least in part due to the impairment in peroxisomal ether-GPs synthesis and that restoration of ether-GPs by OAG treatment can improve TBI outcomes.http://www.sciencedirect.com/science/article/pii/S0022227525000811traumatic brain injury (TBI)lipidether-glycerophospholipidsneurodegeneration |
| spellingShingle | Amir A. Mehrabani-Tabari Nivedita Hegdekar Sabrina Bustos Yulemni Morel Yuanyuan Ji Sazia Arefin Kachi Olivia Pettyjohn-Robin Sagarina Thapa Maya Bhattiprolu Marta M. Lipinski Jace W. Jones Chinmoy Sarkar Peroxisomal ether-glycerophospholipid synthesis is dysregulated after TBI Journal of Lipid Research traumatic brain injury (TBI) lipid ether-glycerophospholipids neurodegeneration |
| title | Peroxisomal ether-glycerophospholipid synthesis is dysregulated after TBI |
| title_full | Peroxisomal ether-glycerophospholipid synthesis is dysregulated after TBI |
| title_fullStr | Peroxisomal ether-glycerophospholipid synthesis is dysregulated after TBI |
| title_full_unstemmed | Peroxisomal ether-glycerophospholipid synthesis is dysregulated after TBI |
| title_short | Peroxisomal ether-glycerophospholipid synthesis is dysregulated after TBI |
| title_sort | peroxisomal ether glycerophospholipid synthesis is dysregulated after tbi |
| topic | traumatic brain injury (TBI) lipid ether-glycerophospholipids neurodegeneration |
| url | http://www.sciencedirect.com/science/article/pii/S0022227525000811 |
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