Sensitivity of the Natriuretic Peptide/cGMP System to Hyperammonaemia in Rat C6 Glioma Cells and GPNT Brain Endothelial Cells

Cells

Rhiannon Strickland¹  VictoriaJ. Lipscomb¹  ImeldaM. McGonnell²  Charlotte Lawson²  Emily Stacey³  Sabah Khan³  Torinn Powles³  RobertC. Fowkes³  J.Sebastian Dennis-Beron³  SamanthaM. Mirczuk³  Michael Worwood³  Matthew Ginley-Hidinger³  JacobT. Regan³  ChristopherJ. Scudder³  MichaelS. Tivers⁴  HolgerA. Volk⁵ 

[1] Clinical Sciences & Services, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire, AL9 7TA UK;Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London, NW1 0TU, UK;Endocrine Signalling Group, Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London, NW1 0TU, UK;Paragon Veterinary Referrals, Paragon Business Village Paragon Way, Red Hall Cres, Wakefield, WF1 2DF, UK;Stiftung Tierärztliche Hochschule Hannover, Klinik für Kleintiere, Bünteweg, 930559 Hannover, Germany;

关键词: natriuretic peptides;    cGMP;    hyperammonaemia;    astrocyte;    neuroendocrinology;    endothelial cells;   

DOI  :  10.3390/cells10020398

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown