Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells
| Autor: | Rhiannon Strickland, Imelda M. McGonnell, Robert C. Fowkes, Holger A. Volk, Victoria Lipscomb, Charlotte Lawson, Matthew Ginley-Hidinger, Christopher J Scudder, Michael Worwood, Jacob T. Regan, J Sebastian Dennis-Beron, Torinn Powles, Samantha M. Mirczuk, Sabah Khan, Michael Tivers, Emily Stacey |
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| Přispěvatelé: | Khan, Sabah [0000-0002-7011-6725], Volk, Holger A [0000-0002-7312-638X], Lipscomb, Victoria J [0000-0001-8427-5885], Fowkes, Robert C [0000-0002-2222-2056], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.drug_class
Central nervous system hyperammonaemia Article Nitric oxide chemistry.chemical_compound astrocyte Natriuretic peptide medicine Animals Hyperammonemia Receptor lcsh:QH301-705.5 Cyclic GMP Chemistry Phosphoric Diester Hydrolases Neurogenesis Phosphodiesterase Brain Natriuretic Peptide C-Type General Medicine Extracellular vesicle Glioma endothelial cells Cell biology Rats cGMP medicine.anatomical_structure lcsh:Biology (General) neuroendocrinology natriuretic peptides extracellular vesicles Astrocyte Signal Transduction |
| Zdroj: | Cells Volume 10 Issue 2 Cells, Vol 10, Iss 398, p 398 (2021) |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells10020398 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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