Cell Proliferation in the Adult Adrenal Medulla: Chromaffin Cells as a Model for Indirect Carcinogenesis

1996 ◽  
pp. 405-411 ◽  
Author(s):  
Arthur S. Tischler
Keyword(s):  
Cell Proliferation ◽  
Adrenal Medulla ◽  
Chromaffin Cells

Immunogold labeling of the calcium binding protein synexin in isolated adrenal chromaffin granules and chromaffin cells

1990 ◽  
Vol 48 (3) ◽  
pp. 952-953
Author(s):  
Gemma A.J. Kuijpers ◽  
Harvey B. Pollard
Keyword(s):  
Adrenal Medulla ◽  
Calcium Binding ◽  
Chromaffin Cells ◽  
Cell Activation ◽  
Structural Information ◽  
Dependent Manner ◽  
Chromaffin Granules ◽  
Immuno Electron Microscopy ◽  
Ultrathin Sections ◽  
Adrenal Chromaffin

Exocytotic fusion of granules in the adrenal medulla chromaffin cell is triggered by a rise in the concentration of cytosolic Ca2+ upon cell activation. The protein synexin, annexin VII, was originally found in the adrenal medulla and has been shown to cause aggregation and to support fusion of chromaffin granules in a Ca2+-dependent manner. We have previously suggested that synexin may there fore play a role in the exocytotic fusion process. In order to obtain more structural information on synexin, we performed immuno-electron microscopy on frozen ultrathin sections of both isolated chromaffin granules and chromaffin cells.Chromaffin granules were isolated from bovine adrenal medulla, and synexin was isolated from bovine lung. Granules were incubated in the presence or absence of synexin (24 μg per mg granule protein) and Ca2+ (1 mM), which induces maximal granule aggregation, in 0.3M sucrose-40m MMES buffer(pH 6.0). Granules were pelleted, washed twice in buffer without synexin and fixed with 2% glutaraldehyde- 2% para formaldehyde in 0.1 M phosphate buffer (GA/PFA) for 30 min. Chromaffin cells were isolated and cultured for 3-5 days, and washed and incubated in Krebs solution with or without 20 uM nicotine. Cells were fixed 90 sec after on set of stimulation with GA/PFA for 30 min. Fixed granule or cell pellets were washed, infiltrated with 2.3 M sucrose in PBS, mounted and frozen in liquid N2.

scholarly journals GIPC2 is an endocrine-specific tumor suppressor gene for both sporadic and hereditary tumors of RET- and SDHB-, but not VHL-associated clusters of pheochromocytoma/paraganglioma

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Yeqing Dong ◽  
Yongsheng Huang ◽  
Chengyan Fan ◽  
Liang Wang ◽  
Ran Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Chromaffin Cells ◽  
Disease Free Survival ◽  
Suppressor Gene ◽  
Adrenal Chromaffin Cell ◽  
Putative Tumor Suppressor Gene ◽  
Mutant Effect ◽  
Hereditary Tumors

AbstractPheochromocytoma/paraganglioma (PPGL) is an endocrine tumor of the chromaffin cells in the adrenal medulla or the paraganglia. Currently, about 70% of PPGLs can be explained by germline or somatic mutations in several broadly expressed susceptibility genes including RET, VHL, and SDHB, while for the remaining, mainly sporadic cases, the pathogenesis is still unclear. Even for known susceptible genes, how mutations in these mostly ubiquitous genes result in tissue-specific pathogenesis remains unanswered, and why RET-mutated tumors almost always occur in the adrenal while SDHB-mutated tumors mostly occur extra-adrenal remains a mystery. By analyzing 22 sporadic PPGLs using SNP 6.0 genotyping arrays combined with expression profiling of 4 normal and 4 tumor tissues, we identified GIPC2, a gene located at 1p31.1 with preferential expression in adrenal and inducible by adrenal glucocorticoid, as a novel putative tumor suppressor gene for PPGLs. Copy number deletion and GIPC2 promoter hypermethylation but not GIPC2 mutation, accompanied with reduced GIPC2 expression, were observed in 39 of 55 PPGLs in our cohort. Examination of a published expression database consisting of 188 PPGLs found little GIPC2 expression in Cluster 1A (SDHx-associated) and Cluster 2A (NF1/RET-associated) tumors, but less pronounced reduction of GIPC2 expression in Cluster 1B (VHL-associated) and Cluster 2B/2C tumors. GIPC2 induced p27, suppressed MAPK/ERK and HIF-1ɑ pathways as well as cancer cell proliferation. Overexpressing GIPC2 in PC12 cells inhibited tumor growth in nude mice. We found GIPC2 interacted with the nucleoprotein NONO and both proteins regulated p27 transcription through the same GGCC box on p27 promoter. Significantly, low expression of both GIPC2 and p27 was associated with shorter disease-free survival time of PPGLs patients in the TCGA database. We found that PPGL-causing mutations in RET and in SDHB could lead to primary rat adrenal chromaffin cell proliferation, ERK activation, and p27 downregulation, all requiring downregulating GIPC2. Notably, the RET-mutant effect required the presence of dexamethasone while the SDHB-mutant effect required its absence, providing a plausible explanation for the tumor location preference. In contrast, the PPGL-predisposing VHL mutations had no effect on proliferation and GIPC2 expression but caused p53 downregulation and reduced apoptosis in chromaffin cells compared with wild-type VHL. Thus, our study raises the importance of cortical hormone in PPGL development, and GIPC2 as a novel tumor suppressor provides a unified molecular mechanism for the tumorigenesis of both sporadic and hereditary tumors of Clusters 1A and 2A concerning SDHB and RET, but not tumors of Cluster 1B concerning VHL and other clusters.

scholarly journals Multipotent peripheral glial cells generate neuroendocrine cells of the adrenal medulla

Science ◽  
2017 ◽  
Vol 357 (6346) ◽  
pp. eaal3753 ◽  
Author(s):  
Alessandro Furlan ◽  
Vyacheslav Dyachuk ◽  
Maria Eleni Kastriti ◽  
Laura Calvo-Enrique ◽  
Hind Abdo ◽  
...  
Keyword(s):  
Adrenal Medulla ◽  
Chromaffin Cells ◽  
Gene Networks ◽  
System Development ◽  
Motor Nerve ◽  
Neuroendocrine Cells ◽  
Molecular Logic ◽  
Large Numbers ◽  
Cell Niche ◽  
Type Specification

Adrenaline is a fundamental circulating hormone for bodily responses to internal and external stressors. Chromaffin cells of the adrenal medulla (AM) represent the main neuroendocrine adrenergic component and are believed to differentiate from neural crest cells. We demonstrate that large numbers of chromaffin cells arise from peripheral glial stem cells, termed Schwann cell precursors (SCPs). SCPs migrate along the visceral motor nerve to the vicinity of the forming adrenal gland, where they detach from the nerve and form postsynaptic neuroendocrine chromaffin cells. An intricate molecular logic drives two sequential phases of gene expression, one unique for a distinct transient cellular state and another for cell type specification. Subsequently, these programs down-regulate SCP-gene and up-regulate chromaffin cell–gene networks. The AM forms through limited cell expansion and requires the recruitment of numerous SCPs. Thus, peripheral nerves serve as a stem cell niche for neuroendocrine system development.

Interactions Between Bovine Adrenal Medulla Endothelial and Chromaffin Cells

1998 ◽  
pp. 91-107 ◽  
Author(s):  
Fernando F. Vargas ◽  
Soledad Calvo ◽  
Raul Vinet ◽  
Eduardo Rojas
Keyword(s):  
Adrenal Medulla ◽  
Chromaffin Cells ◽  
Bovine Adrenal Medulla

scholarly journals Immunohistochemical evidence for the presence of a vasoactive intestinal peptide, neuropeptide Y and substance P in rat adrenal medulla after heat stress

2012 ◽  
Vol 64 (1) ◽  
pp. 7-13
Author(s):  
Dragana Petrovic-Kosanovic ◽  
Vesna Koko
Keyword(s):  
Heat Stress ◽  
Substance P ◽  
Neuropeptide Y ◽  
Vasoactive Intestinal Peptide ◽  
Adrenal Medulla ◽  
Chromaffin Cells ◽  
Ganglion Cells ◽  
Nerve Fibers ◽  
Acute Heat Stress ◽  
Immunohistochemical Evidence

Immunohistochemistry revealed the presence of VIP-, NPY- and SP-immunoreactivity in the rat adrenal medulla. VIP- and NPY-immunoreactivity was detected in chromaffin and ganglion cells and in nerve fibers, but SP-immunoreactivity was found only in chromaffin cells. After acute heat stress, VIP- and NPY- immunoreactivities in cells and nerve fibers were reduced, probably as a result of the release of these peptides with catecholamines. The absence of SP-immunoreactive ganglion cells in the adrenal medulla suggests that the SP-immunoreactive nerve fibers are extrinsic in origin.

High-intensity training induces EIB in rats through neuron transdifferentiation of adrenal medulla chromaffin cells

2013 ◽  
Vol 304 (9) ◽  
pp. L602-L612 ◽  
Author(s):  
Ruoxi He ◽  
Juntao Feng ◽  
Qiufen Xun ◽  
Qingwu Qin ◽  
Chengping Hu
Keyword(s):  
Adrenal Medulla ◽  
Chromaffin Cells ◽  
Cell Structure ◽  
Fold Increase ◽  
Inflammatory Cells ◽  
Whole Body ◽  
Moderate Intensity ◽  
Sprague Dawley ◽  
Exercise Interventions ◽  
Intensity Training

A high prevalence of exercise-induced bronchoconstriction (EIB) can be found in elite athletes, but the underlying mechanisms remain elusive. Airway responsiveness, NGF and epinephrine (EPI) levels, and chromaffin cell structure in high- (HiTr) and moderate-intensity training (MoTr) rats with or without ovalbumin (OVA) sensitization were measured in a total of 120 male Sprague-Dawley rats. The expression of NGF-associated genes in rat adrenal medulla was tested. Both HiTr and OVA intervention significantly increased airway resistance to aerosolized methacholine measured by whole body plethysmography. HiTr significantly increased inflammatory reaction in the lung with a major increase in peribronchial lymphocyte infiltration, whereas OVA significantly increased the infiltration of various inflammatory cells with an over 10-fold increase in eosinophil level in bronchoalveolar lavage. Both HiTr and OVA intervention upregulated circulating NGF level and peripherin level in adrenal medulla, but downregulated phenylethanolamine N-methyl transferase level in adrenal medulla and circulating EPI level. HiTr + OVA and HiTr + ExhEx (exhaustive exercise) interventions significantly enhanced most of the HiTr effects. The elevated NGF level was significantly associated with neuronal conversion of adrenal medulla chromaffin cells (AMCC). The levels of p-Erk1/2, JMJD3, and Mash1 were significantly increased, but the levels of p-p38 and p-JNK were significantly decreased in adrenal medulla in HiTr and OVA rats. Injection of NGF antiserum and moderate-intensity training reversed these changes observed in HiTr and/or OVA rats. Our study suggests that NGF may play a vital role in the pathogenesis of EIB by inducing neuron transdifferentiation of AMCC via MAPK pathways and subsequently decreasing circulating EPI.

Changes in nucleoli and nucleolar fibrillar centres of chromaffin cells in rat adrenal medulla over a 24-hour period: an ultrastructural and stereological analysis

1985 ◽  
Vol 77 (1) ◽  
pp. 255-262
Author(s):  
A. Robaglia ◽  
R. Seite
Keyword(s):  
Adrenal Medulla ◽  
Chromaffin Cells ◽  
Extreme Values ◽  
Sympathetic Neurons ◽  
Cellular Level ◽  
Temporal Organization ◽  
Free Access ◽  
Stereological Analysis ◽  
The Mean ◽  
Two Parameters

A stereological and ultrastructural study was performed on the nucleoli of the adrenal medulla chromaffin cells of rats exposed to a standardized 12 h light/12 h dark cycle with free access to food and water. The animals were killed three at a time, every 4 h during the 24-h span and fixed by intracardiac perfusion. In these reticulated nucleoli, the stereological analysis over a 24-h period showed a variation dependent on the time of killing for the two parameters investigated, the mean nucleolar volume, Vnu, and the mean volume of the fibrillar centres, Vfc(nu). The minimal value occurred at 0300 h (dark span) and the maximal one at 0700 h (at the onset of the light span). Between these two extreme values, Vnu increased 1.8-fold and Vfc(nu) 5.3-fold. These data are compared with a previous description from our laboratory of circadian rhythm in nucleoli of sympathetic neurons of superior cervical ganglion in the same animals. Analogies and differences are pointed out, but apart from these considerations the present study provides a new example of temporal organization at the cellular level in the organelle involved in ribosomal RNA synthesis and ribosome assembly.

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