Regulation of angiotensinogen by angiotensin II in mouse primary astrocyte cultures

J. Neurochem. (2011) 119, 18–26. Astrocytes are the major source of angiotensinogen in the brain and play an important role in the brain renin‐angiotensin system. Regulating brain angiotensinogen production alters blood pressure and fluid and electrolyte homeostasis. In turn, several physiological a...

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Vydáno v:	Journal of neurochemistry Ročník 119; číslo 1; s. 18 - 26
Hlavní autoři:	O’Callaghan, E. L., Bassi, J. K., Porrello, E. R., Delbridge, L. M. D., Thomas, W. G., Allen, A. M.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Oxford, UK Blackwell Publishing Ltd 01.10.2011 Wiley-Blackwell
Témata:	Adenoviridae - genetics Angiotensin Angiotensin II Angiotensin II - physiology Angiotensin II Type 1 Receptor Blockers - pharmacology Angiotensin receptors angiotensinogen Angiotensinogen - metabolism Animals Astrocytes Astrocytes - drug effects Astrocytes - metabolism Benzimidazoles - pharmacology Biological and medical sciences Blood pressure Brain Brain - cytology Brain Chemistry - physiology cardiomyocytes Cell culture Cells, Cultured cultures Data processing Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Dexamethasone - pharmacology Expression vectors Feedback, Physiological Fundamental and applied biological sciences. Psychology G protein‐coupled receptor Gene expression Hepatocytes Homeostasis Imidazoles - pharmacology Immunocytochemistry Immunohistochemistry Inositol Phosphates - physiology Isolated neuron and nerve. Neuroglia Liver - drug effects Liver - metabolism Medical sciences Mice Mice, Inbred C57BL Neonates Neurochemistry Neurology Polymerase chain reaction Proteins Pyridines - pharmacology qPCR Receptors, Angiotensin - metabolism Reverse Transcriptase Polymerase Chain Reaction Rodents Signal transduction Signal Transduction - physiology Tetrazoles - pharmacology Vertebrates: nervous system and sense organs Neonatal Liver Neuroglia Central nervous system Homeostasis angiotensinogen Encephalon Myocyte Hepatocyte Primary culture Blood pressure qPCR Angiotensin II G protein-coupled receptor Digestive system Rodentia Astrocyte Angiotensin receptor Vertebrata Renin angiotensin system Mammalia Electrolyte Mouse cultures Hemodynamics astrocytes
ISSN:	0022-3042, 1471-4159, 1471-4159
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Shrnutí:	J. Neurochem. (2011) 119, 18–26. Astrocytes are the major source of angiotensinogen in the brain and play an important role in the brain renin‐angiotensin system. Regulating brain angiotensinogen production alters blood pressure and fluid and electrolyte homeostasis. In turn, several physiological and pathological manipulations alter expression of angiotensinogen in brain. Surprisingly, little is known about the factors that regulate astrocytic expression of angiotensinogen. There is evidence that angiotensinogen production in both hepatocytes and cardiac myocytes can be positively regulated via the angiotensin type 1 receptor, but this effect has not yet been studied in astrocytes. Therefore, the aim of this project was to establish whether angiotensin II modulates angiotensinogen production in brain astrocytes. Primary astrocyte cultures, prepared from neonatal C57Bl6 mice, expressed angiotensinogen measured by immunocytochemistry and real‐time PCR. Using a variety of approaches we were unable to identify angiotensin receptors on cultured astrocytes. Exposure of cultured astrocytes to angiotensin II also did not affect angiotensinogen expression. When astrocyte cultures were transduced with the angiotensin type 1A receptor, using adenoviral vectors, angiotensin II induced a robust down‐regulation (91.4% ± 1.8%, p < 0.01, n = 4) of angiotensinogen gene expression. We conclude that receptors for angiotensin II are present in extremely low levels in astrocytes, and that this concurs with available data in vivo. The signaling pathways activated by the angiotensin type 1A receptor are negatively coupled to angiotensinogen expression and represent a powerful pathway for decreasing expression of this protein, potentially via signaling pathways coupled to Gαq/11.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0022-3042 1471-4159 1471-4159
DOI:	10.1111/j.1471-4159.2011.07406.x