Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells
C-type natriuretic peptide (CNP) is the major natriuretic peptide of the central nervous system and acts via its selective guanylyl cyclase-B (GC-B) receptor to regulate cGMP production in neurons, astrocytes and endothelial cells. CNP is implicated in the regulation of neurogenesis, axonal bifurcat...
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| Materiálatiipa: | Artihkal |
| Giella: | English |
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MDPI AG
2021-02-01
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| Ráidu: | Cells |
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| Liŋkkat: | https://www.mdpi.com/2073-4409/10/2/398 |
| _version_ | 1827589178519453696 |
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| author | Jacob T. Regan Samantha M. Mirczuk Christopher J. Scudder Emily Stacey Sabah Khan Michael Worwood Torinn Powles J. Sebastian Dennis-Beron Matthew Ginley-Hidinger Imelda M. McGonnell Holger A. Volk Rhiannon Strickland Michael S. Tivers Charlotte Lawson Victoria J. Lipscomb Robert C. Fowkes |
| author_facet | Jacob T. Regan Samantha M. Mirczuk Christopher J. Scudder Emily Stacey Sabah Khan Michael Worwood Torinn Powles J. Sebastian Dennis-Beron Matthew Ginley-Hidinger Imelda M. McGonnell Holger A. Volk Rhiannon Strickland Michael S. Tivers Charlotte Lawson Victoria J. Lipscomb Robert C. Fowkes |
| author_sort | Jacob T. Regan |
| collection | DOAJ |
| description | C-type natriuretic peptide (CNP) is the major natriuretic peptide of the central nervous system and acts via its selective guanylyl cyclase-B (GC-B) receptor to regulate cGMP production in neurons, astrocytes and endothelial cells. CNP is implicated in the regulation of neurogenesis, axonal bifurcation, as well as learning and memory. Several neurological disorders result in toxic concentrations of ammonia (hyperammonaemia), which can adversely affect astrocyte function. However, the relationship between CNP and hyperammonaemia is poorly understood. Here, we examine the molecular and pharmacological control of CNP in rat C6 glioma cells and rat GPNT brain endothelial cells, under conditions of hyperammonaemia. Concentration-dependent inhibition of C6 glioma cell proliferation by hyperammonaemia was unaffected by CNP co-treatment. Furthermore, hyperammonaemia pre-treatment (for 1 h and 24 h) caused a significant inhibition in subsequent CNP-stimulated cGMP accumulation in both C6 and GPNT cells, whereas nitric-oxide-dependent cGMP accumulation was not affected. CNP-stimulated cGMP efflux from C6 glioma cells was significantly reduced under conditions of hyperammonaemia, potentially via a mechanism involving changed in phosphodiesterase expression. Hyperammonaemia-stimulated ROS production was unaffected by CNP but enhanced by a nitric oxide donor in C6 cells. Extracellular vesicle production from C6 cells was enhanced by hyperammonaemia, and these vesicles caused impaired CNP-stimulated cGMP signalling in GPNT cells. Collectively, these data demonstrate functional interaction between CNP signalling and hyperammonaemia in C6 glioma and GPNT cells, but the exact mechanisms remain to be established. |
| first_indexed | 2024-03-09T00:51:56Z |
| format | Article |
| id | doaj.art-d3b5d5bf11594335bcd0792cf4403ebc |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T00:51:56Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-d3b5d5bf11594335bcd0792cf4403ebc2023-12-11T17:10:06ZengMDPI AGCells2073-44092021-02-0110239810.3390/cells10020398Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial CellsJacob T. Regan0Samantha M. Mirczuk1Christopher J. Scudder2Emily Stacey3Sabah Khan4Michael Worwood5Torinn Powles6J. Sebastian Dennis-Beron7Matthew Ginley-Hidinger8Imelda M. McGonnell9Holger A. Volk10Rhiannon Strickland11Michael S. Tivers12Charlotte Lawson13Victoria J. Lipscomb14Robert C. Fowkes15Endocrine Signalling Group, Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UKEndocrine Signalling Group, Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UKEndocrine Signalling Group, Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UKEndocrine Signalling Group, Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UKEndocrine Signalling Group, Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UKEndocrine Signalling Group, Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UKEndocrine Signalling Group, Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UKEndocrine Signalling Group, Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UKEndocrine Signalling Group, Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UKDepartment of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UKStiftung Tierärztliche Hochschule Hannover, Klinik für Kleintiere, Bünteweg, 930559 Hannover, GermanyClinical Sciences & Services, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UKParagon Veterinary Referrals, Paragon Business Village Paragon Way, Red Hall Cres, Wakefield WF1 2DF, UKDepartment of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UKClinical Sciences & Services, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UKEndocrine Signalling Group, Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UKC-type natriuretic peptide (CNP) is the major natriuretic peptide of the central nervous system and acts via its selective guanylyl cyclase-B (GC-B) receptor to regulate cGMP production in neurons, astrocytes and endothelial cells. CNP is implicated in the regulation of neurogenesis, axonal bifurcation, as well as learning and memory. Several neurological disorders result in toxic concentrations of ammonia (hyperammonaemia), which can adversely affect astrocyte function. However, the relationship between CNP and hyperammonaemia is poorly understood. Here, we examine the molecular and pharmacological control of CNP in rat C6 glioma cells and rat GPNT brain endothelial cells, under conditions of hyperammonaemia. Concentration-dependent inhibition of C6 glioma cell proliferation by hyperammonaemia was unaffected by CNP co-treatment. Furthermore, hyperammonaemia pre-treatment (for 1 h and 24 h) caused a significant inhibition in subsequent CNP-stimulated cGMP accumulation in both C6 and GPNT cells, whereas nitric-oxide-dependent cGMP accumulation was not affected. CNP-stimulated cGMP efflux from C6 glioma cells was significantly reduced under conditions of hyperammonaemia, potentially via a mechanism involving changed in phosphodiesterase expression. Hyperammonaemia-stimulated ROS production was unaffected by CNP but enhanced by a nitric oxide donor in C6 cells. Extracellular vesicle production from C6 cells was enhanced by hyperammonaemia, and these vesicles caused impaired CNP-stimulated cGMP signalling in GPNT cells. Collectively, these data demonstrate functional interaction between CNP signalling and hyperammonaemia in C6 glioma and GPNT cells, but the exact mechanisms remain to be established.https://www.mdpi.com/2073-4409/10/2/398natriuretic peptidescGMPhyperammonaemiaastrocyteneuroendocrinologyendothelial cells |
| spellingShingle | Jacob T. Regan Samantha M. Mirczuk Christopher J. Scudder Emily Stacey Sabah Khan Michael Worwood Torinn Powles J. Sebastian Dennis-Beron Matthew Ginley-Hidinger Imelda M. McGonnell Holger A. Volk Rhiannon Strickland Michael S. Tivers Charlotte Lawson Victoria J. Lipscomb Robert C. Fowkes Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells Cells natriuretic peptides cGMP hyperammonaemia astrocyte neuroendocrinology endothelial cells |
| title | Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells |
| title_full | Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells |
| title_fullStr | Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells |
| title_full_unstemmed | Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells |
| title_short | Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells |
| title_sort | sensitivity of the natriuretic peptide cgmp system to hyperammonaemia in rat c6 glioma cells and gpnt brain endothelial cells |
| topic | natriuretic peptides cGMP hyperammonaemia astrocyte neuroendocrinology endothelial cells |
| url | https://www.mdpi.com/2073-4409/10/2/398 |
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