Impact of chromogranin a deficiency on catecholamine storage, catecholamine granule morphology and chromaffin cell energy metabolism in vivo
Open accessAbstract
Chromogranin A (CgA) is a prohormone and granulogenic factor in neuroendocrine tissues with a regulated secretory pathway. The impact of CgA depletion on secretory granule formation has been previously demonstrated in cell culture. However, studies linking the structural effects of CgA deficiency with secretory performance and cell metabolism in the adrenomedullary chromaffin cells in vivo have not previously been reported. Adrenomedullary content of the secreted adrenal catecholamines norepinephrine (NE) and epinephrine (EPI) was decreased 30-40 % in Chga-KO mice. Quantification of NE and EPI-storing dense core (DC) vesicles (DCV) revealed decreased DCV numbers in chromaffin cells in Chga-KO mice. For both cell types, the DCV diameter in Chga-KO mice was less (100-200 nm) than in WT mice (200-350 nm). The volume density of the vesicle and vesicle number was also lower in Chga-KO mice. Chga-KO mice showed an ~47 % increase in DCV/DC ratio, implying vesicle swelling due to increased osmotically active free catecholamines. Upon challenge with 2 U/kg insulin, there was a diminution in adrenomedullary EPI, no change in NE and a very large increase in the EPI and NE precursor dopamine (DA), consistent with increased catecholamine biosynthesis during prolonged secretion. We found dilated mitochondrial cristae, endoplasmic reticulum and Golgi complex, as well as increased synaptic mitochondria, synaptic vesicles and glycogen granules in Chga-KO mice compared to WT mice, suggesting that decreased granulogenesis and catecholamine storage in CgA-deficient mouse adrenal medulla is compensated by increased VMAT-dependent catecholamine update into storage vesicles, at the expense of enhanced energy expenditure by the chromaffin cell.
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Chga is critical for epinephrine condensation in dense-core granules.
“Chga is critical for epinephrine condensation in DCGs (Pasqua et al., 2016).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Pasqua et al., 2016
Chga regulates the biogenesis of catecholamine-containing DCGs in the adrenal gland.
“Chga has been shown to regulate the biogenesis of catecholamine-containing DCGs in the adrenal gland (Díaz-Vera et al., 2012; Kim et al., 2001; Pasqua et al., 2016).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Pasqua et al., 2016
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Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells
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- Authors
- Pasqua, T., Mahata, S., Bandyopadhyay, G. K., Biswas, A., Perkins, G. A., Sinha-Hikim, A. P., Goldstein, D. S., Eiden, L. E., & Mahata, S. K.
- Affiliations
- University of California San Diego (US)
- California Institute of Technology (US)
- National Institutes of Health (US)
- Corresponding author
- Mahata, Sumana
- Mahata, Sushil K.
- ORCID
- Venue
- Cell and Tissue Research
- Published
- 2015-11-16
- Volume
- 363
- Issue
- 3
- Pages
- 693-712
- ISSN
- 0302-766X (ISSN-L)
- 1432-0878
- PMC
- PMC5585018
- OpenAlex
- W2173900167
- Cited by
- 53
- References
- 85
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 2 · 2023: 7 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 5 · 2017: 4 · 2016: 5
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Update notices
- correction (2016-01-26)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell and Tissue Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Archive of Doctoral Theses and Digital Collections (University of Calabria) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (P41GM103412)
- National Institute of Neurological Disorders and Stroke (ZIANS003033)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- chromogranin A, catecholamine storage, chromaffin cells, adrenal medulla, dense core vesicles, catecholamine synthesis, norepinephrine, epinephrine, dopamine, mitochondrial cristae, energy metabolism, volumetric modulated arc therapy, regulated secretion
- MeSH terms
- Adrenal Glands, Animals, Catecholamines, Chromaffin Granules, Dopamine, Endocytosis, Endoplasmic Reticulum, Energy Metabolism, Epinephrine, Exocytosis, Glucose, Glycogen, Golgi Apparatus, Humans, Insulin, Mice, Inbred C57BL, Mitochondria, Norepinephrine, Splanchnic Nerves, Synaptic Vesicles, Blotting, Western, Mice, Knockout, Chromogranin A
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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