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Astrocytes synthesize angiotensinogen in brain
R L Stornetta1, C L Hawelu-Johnson, P G Guyenet
1Department of Pharmacology, University of Virginia School of Medicine, Charlottesville 22908.
Science (New York, N.Y.)
|December 9, 1988
Summary
Angiotensinogen, a key protein precursor, is synthesized by glial cells in the rat brain, not neurons. This finding clarifies the cellular origin of angiotensinogen, impacting our understanding of brain signaling pathways.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Angiotensinogen is a precursor protein involved in the renin-angiotensin system.
- The cellular localization of angiotensinogen synthesis in the brain has been previously unclear.
- Understanding angiotensinogen's origin is crucial for brain function and disease research.
Purpose of the Study:
- To identify the specific cell types responsible for angiotensinogen mRNA expression in the rat brain.
- To differentiate between neuronal and glial synthesis of angiotensinogen.
Main Methods:
- In situ hybridization using radiolabeled RNA probes and oligonucleotide probes.
- Immunocytochemical detection of glial fibrillary acidic protein (GFAP) for astrocytes.
- Immunocytochemical detection of microtubule-associated protein 2 (MAP-2) for neurons.
- Autoradiography to visualize silver grain localization.
Main Results:
- Angiotensinogen mRNA was primarily localized to cells expressing GFAP, indicating astrocytes.
- A significant association between silver grains (indicating mRNA) and GFAP-reactive cells was observed.
- Few or no silver grains were found associated with MAP-2-reactive neurons.
- These findings strongly suggest that glial cells, specifically astrocytes, are the main sites of angiotensinogen synthesis in the rat brain.
Conclusions:
- Angiotensinogen is synthesized by glial cells (astrocytes) in the rat brain.
- This contrasts with the known synthesis of other neuropeptide precursors, which often occurs in neurons.
- The study clarifies the cellular source of angiotensinogen, providing a foundation for further research into its role in the brain.