CaltechAUTHORS
  A Caltech Library Service

Impact of Chromogranin A deficiency on catecholamine storage, catecholamine granule morphology and chromaffin cell energy metabolism in vivo

Pasqua, Teresa and Mahata, Sumana and Bandyopadhyay, Gautam K. and Biswas, Angshuman and Perkins, Guy A. and Sinha-Hikim, Amiya P. and Goldstein, David S. and Eiden, Lee E. and Mahata, Sushil K. (2016) Impact of Chromogranin A deficiency on catecholamine storage, catecholamine granule morphology and chromaffin cell energy metabolism in vivo. Cell and Tissue Research, 363 (3). pp. 693-712. ISSN 0302-766X. doi:10.1007/s00441-015-2316-3. https://resolver.caltech.edu/CaltechAUTHORS:20151123-131003229

[img] PDF (Erratum) - Erratum
See Usage Policy.

162kB

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20151123-131003229

Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1007/s00441-015-2316-3DOIArticle
http://link.springer.com/article/10.1007%2Fs00441-015-2316-3PublisherArticle
http://dx.doi.org/10.1007/s00441-016-2362-5ErrataErratum
http://link.springer.com/article/10.1007%2Fs00441-016-2362-5ErrataErratum
Additional Information:© 2015 Springer-Verlag Berlin Heidelberg. Received: 12 August 2015; Accepted: 16 October 2015. Transmission Electron Microscopy was conducted at the Cellular & Molecular Medicine Electron Microscopy Core Facility at UCSD. A Research Career Scientist Award from the Department of Veterans Affairs supports S.K.M. Mahata’s personal fund and UCSD Academic Senate Grant (RO091B) supported this work. Teresa Pasqua and Sumana Mahata contributed equally to this work. The authors have nothing to declare.
Errata:Erratum to: Impact of Chromogranin A deficiency on catecholamine storage, catecholamine granule morphology and chromaffin cell energy metabolism in vivo Teresa Pasqua, Sumana Mahata, Gautam K. Bandyopadhyay, Angshuman Biswas, Guy A. Perkins, Amiya P. Sinha-Hikim, David S. Goldstein, Lee E. Eiden, Sushil K. Mahata Cell and Tissue Research March 2016, Volume 363, Issue 3, pp 823
Funders:
Funding AgencyGrant Number
Department of Veterans AffairsUNSPECIFIED
University of California San DiegoRO091B
Subject Keywords:Norepinephrine; Epinephrine; Dense core vesicle; Synaptic vesicle; Mitochondria
Issue or Number:3
DOI:10.1007/s00441-015-2316-3
Record Number:CaltechAUTHORS:20151123-131003229
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20151123-131003229
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:62334
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:23 Nov 2015 21:37
Last Modified:10 Nov 2021 23:01

Repository Staff Only: item control page