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J M Trifaro - One of the best experts on this subject based on the ideXlab platform.
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Chromaffin Cell f actin disassembly and potentiation of catecholamine release in response to protein kinase c activation by phorbol esters is mediated through myristoylated alanine rich c kinase substrate phosphorylation
Journal of Biological Chemistry, 2001Co-Authors: Sergio D Rose, Tatiana Lejen, Li Zhang, J M TrifaroAbstract:Abstract The large majority of Chromaffin vesicles are excluded from the plasma membrane by a cortical F-actin network. Treatment of Chromaffin Cells with phorbol 12-myristate 13-acetate produces disassembly of cortical F-actin, increasing the number of vesicles at release sites (Vitale, M. L., Seward, E. P., and Trifaro, J. M. (1995) Neuron 14, 353–363). Here, we provide evidence for involvement of myristoylated alanine-rich protein kinase C substrate (MARCKS), a protein kinase C substrate, in Chromaffin Cell secretion. MARCKS binds and cross-links F-actin, the latter is inhibited by protein kinase C-induced MARCKS phosphorylation. MARCKS was found in Chromaffin Cells by immunoblotting. MARCKS was also detected by immunoprecipitation. In intact or permeabilized Cells MARCKS phosphorylation increased upon stimulation with 10−7 m phorbol 12-myristate 13-acetate. This was accompanied by cortical F-actin disassembly and potentiation of secretion. MARCKS phosphorylation, cortical F-actin disassembly, and potentiation of Ca2+-evoked secretion were inhibited by a peptide (MARCKS phosphorylation site domain sequence (MPSD)) with amino acid sequence corresponding to MARCKS phosphorylation site. MPSD was phosphorylated in the process. A similar peptide (alanine-substituted phosphorylated site domain) with four serine residues of MPSD substituted by alanines was ineffective. These results provide the first evidence for MARCKS involvement in Chromaffin Cell secretion and suggest that regulation of cortical F-actin cross-linking might be involved in this process.
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two pathways control Chromaffin Cell corticalf actin dynamics during exocytosis
Biochimie, 2000Co-Authors: J M Trifaro, Sergio D Rose, Tatiana Lejen, Abdelbaset ElzagallaaiAbstract:Abstract Neurosecretory Cells including Chromaffin Cells possess a mesh of filamentous actin underneath the plasma membrane. We have proposed that the F-actin network acts as a barrier to the secretory vesicles blocking their access to exocytotic sites at the plasma membrane. Disassembly of cortical F-actin in Chromaffin Cells in response to stimulation is thought to allow the free movement of secretory vesicles to exocytotic sites. Moreover, experiments by us using morphometric analysis of resting and stimulated Chromaffin Cells together with membrane capacitance measurements have shown that cortical F-actin controls the traffic of vesicles from the vesicle reserve compartment to the release-ready vesicle compartment. The dynamics of the cortical F-actin is controlled by two pathways: A) stimulation-induced Ca 2+ entry and scinderin activation; and B) protein kinase C (PKC) activation and MARCKS (myristoylated alanine-rich C kinase substrate) phosphorylation. When Chromaffin Cells are stimulated through nicotinic receptors, cortical F-actin disassembly is mainly through the intervention of pathway A, since in the presence of PKC inhibitors, F-actin disassembly in response to cholinergic stimulation is only blocked by 20%. Pathway A involves the activation of scinderin by Ca 2+ with a consequent F-actin severing. Pathway B is fully activated by phorbol esters and in this case PKC blockers inhibit by 100% the disruption of cortical F-actin. This pathway operates through MARCKS. A peptide with amino acid sequence corresponding to the phosphorylation site domain of MARCKS, which also corresponds to its actin binding site, blocks PMA potentiation of Ca 2+ -induced catecholamine release. The results suggest that under physiological conditions (i.e., nicotinic receptor stimulation) pathway A is the principal mechanism for the control of cortical F-actin dynamic changes.
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molecular cloning and functional expression of Chromaffin Cell scinderin indicates that it belongs to the family of ca2 dependent f actin severing proteins
Molecular and Cellular Biochemistry, 1994Co-Authors: M G Marcu, M L Vitale, Rodriguez A Del Castillo, J M TrifaroAbstract:Scienderin is a Ca+-dependent actin filament severing protein present in Chromaffin Cells, platelets and a variety of secretory Cells. It has been suggested that scinderin is involved in Chromaffin Cell F-actin dynamics and that this actin network controls the delivery of secretory vesicles to plasma membrane exocytotic sites. Moreover, scinderin redistribution and activity may be regulated by pH and Ca2+ in resting and stimulated Cells. Here we describe the molecular cloning, the nucleotide sequence and the expression of bovine Chromaffin Cell scinderin cDNA. The fusion protein obtained cross-reacts with native scinderin antibodies and binds phosphatidylserine (PS), phosphatidylinositol 4,5-bisphosphate (PIP2) and actin in a Ca+-dependent manner. Antibodies raised against the fusion protein produced the same Cellular staining patterns for scinderin as anti-native scinderin. Nucleotide and amino acid sequence analysis indicate that scinderin has six domains each containing three internal sequence motifs, two actin and two PIP2 binding sites and has 63 and 53% homology with gelsolin and villin. These data indicate that scinderin is a novel member of the family of Ca2+-dependent F-actin severing proteins which includes gelsolin and villin.
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dynamic changes in Chromaffin Cell cytoskeleton as prelude to exocytosis
Molecular Neurobiology, 1992Co-Authors: J M Trifaro, Rodriguez A Del Castillo, M L VitaleAbstract:Earlier work by us as well as others has demonstrated that filamentous actin is mainly localized in the cortical surface of Chromaffin Cell. This F-actin network acts as a barrier to the Chromaffin granules, impeding their contact with the plasma membrane. Chromaffin granules contain α-actinin, an anchorage protein that mediates F-actin association with these vesicles. Consequently, Chromaffin granules crosslink and stabilize F-actin networks. Stimulation of Chromaffin Cell produces disassembly of F-actin and removal of the barrier. This interpretation is based on: (1) Cytochemical experiments with rhodamine-labeled phalloidin indicated that in resting Chromaffin Cells, the F-actin network is visualized as a strong cortical fluorescent ring; (2) Nicotinic receptor stimulation produced fragmentation of this fluorescent ring, leaving Chromaffin Cell cortical areas devoid of fluorescence; and (3) These changes are accompanied by a decrease in F-actin, a concomitant increase in G-actin, and a decrease in the F-actin associated with the Chromaffin Cell cytoskeleton (DNAse I assay). We also have demonstrated the presence in Chromaffin Cells of gelsolin and scinderin, two Ca2+-dependent actin filament-severing proteins, and suggested that Chromaffin Cell stimulation activates scinderin with the consequent disruption of F-actin networks. Scinderin, a protein recently isolated in our laboratory, is restricted to secretory Cells and is present mainly in the cortical Chromaffin Cell cytoplasm. Scinderin, which is structurally different from gelsolin (different pIs, amino acid composition, peptide maps, and so on), decreases the viscosity of actin gels as a result of its F-actin-severing properties, as demonstrated by electron microscopy. Stimulation of Chromaffin Cells either by nicotine (10 μM) or high K+ (56 mM) produces a redistribution of subplasmalemmal scinderin and actin disassembly, which preceded exocytosis. The redistribution of scinderin and exocytosis is Ca2+-dependent and is not mediated by muscarinic receptors. Furthermore, our cytochemical experiments demonstrate that Chromaffin Cell stimulation produces a concomitant and similar redistribution of scinderin (fluorescein-labeled antibody) and F-actin (rhodamine phalloidin fluorescence), suggesting a functional interaction between these two proteins. Stimulation-induced redistribution of scinderin and F-actin disassembly would produce subplasmalemmal areas of decreased cytoplasmic viscosity and increased mobility for Chromaffin granules. Exocytosis sites, evaluated by antidopamine-β-hydroxylase (anti-DβH) surface staining, are preferentially localized in plasma membrane areas devoid of F-actin.
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cortical filamentous actin disassembly and scinderin redistribution during Chromaffin Cell stimulation precede exocytosis a phenomenon not exhibited by gelsolin
Journal of Cell Biology, 1991Co-Authors: M L Vitale, Rodriguez A Del Castillo, L Tchakarov, J M TrifaroAbstract:Immunofluorescence and cytochemical studies have demonstrated that filamentous actin is mainly localized in the cortical surface of the Chromaffin Cell. It has been suggested that these actin filament networks act as a barrier to the secretory granules, impeding their contact with the plasma membrane. Stimulation of Chromaffin Cells produces a disassembly of actin filament networks, implying the removal of the barrier. The presence of gelsolin and scinderin, two Ca(2+)-dependent actin filament severing proteins, in the cortical surface of the Chromaffin Cells, suggests the possibility that Cell stimulation brings about activation of one or more actin filament severing proteins with the consequent disruption of actin networks. Therefore, biochemical studies and fluorescence microscopy experiments with scinderin and gelsolin antibodies and rhodamine-phalloidin, a probe for filamentous actin, were performed in cultured Chromaffin Cells to study the distribution of scinderin, gelsolin, and filamentous actin during Cell stimulation and to correlate the possible changes with catecholamine secretion. Here we report that during nicotinic stimulation or K(+)-evoked depolarization, subcortical scinderin but not gelsolin is redistributed and that this redistribution precedes catecholamine secretion. The rearrangement of scinderin in patches is mediated by nicotinic receptors. Cell stimulation produces similar patterns of distribution of scinderin and filamentous actin. However, after the removal of the stimulus, the recovery of scinderin cortical pattern of distribution is faster than F-actin reassembly, suggesting that scinderin is bound in the cortical region of the Cell to a component other than F-actin. We also demonstrate that peripheral actin filament disassembly and subplasmalemmal scinderin redistribution are calcium-dependent events. Moreover, experiments with an antibody against dopamine-beta-hydroxylase suggest that exocytosis sites are preferentially localized to areas of F-actin disassembly.
Nathalie C Guerineau - One of the best experts on this subject based on the ideXlab platform.
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cholinergic and peptidergic neurotransmission in the adrenal medulla a dynamic control of stimulus secretion coupling
Iubmb Life, 2020Co-Authors: Nathalie C GuerineauAbstract:Synaptic neurotransmission at the splanchnic nerve-Chromaffin Cell synapse is a chief element of the stimulus-secretion coupling in the adrenal medullary tissue, managing and regulating the secretion of catecholamines. Making the state of play more intricate than initially envisioned, the synaptic vesicles of nerve terminals innervating the medulla contain various compounds, including various neurotransmitters and neuropeptides. Under basal conditions associated with a low splanchnic nerve discharge rate, neurotransmission is ensured by the synaptic release of the primary neurotransmitter acetylcholine (ACh). Under sustained and repetitive stimulations of the splanchnic nerve, as triggered in response to stressors, the synaptic release of neuropeptides, such as the pituitary adenylate cyclase-activating polypeptide PACAP, supplants ACh release. The anatomical and functional changes that occur presynaptically at the preganglionic splanchnic nerve, combined with changes occurring postsynaptically at nicotinic acetylcholine receptors (nAChRs), confer the adrenomedullary synapses a solid and persistent aptitude to functional remodeling, from birth to aging. The present review focuses on the composite cholinergic and noncholinergic nature of neurotransmission occurring at the splanchnic nerve-Chromaffin Cell synapse and its remodeling in response to physiological or pathological stimuli.
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Functional Chromaffin Cell Plasticity in Response to Stress: Focus on Nicotinic, Gap Junction, and Voltage-Gated Ca^2+ Channels
Journal of Molecular Neuroscience, 2012Co-Authors: Nathalie C Guerineau, Michel G Desarmenien, Valentina Carabelli, Emilio CarboneAbstract:An increase in circulating catecholamines constitutes one of the mechanisms whereby human body responds to stress. In response to chronic stressful situations, the adrenal medullary tissue exhibits crucial morphological and functional changes that are consistent with an improvement of Chromaffin Cell stimulus–secretion coupling efficiency. Stimulus–secretion coupling encompasses multiple intraCellular (Chromaffin Cell excitability, Ca^2+ signaling, exocytosis, endocytosis) and interCellular pathways (splanchnic nerve-mediated synaptic transmission, paracrine and endocrine communication, gap junctional coupling), each of them being potentially subjected to functional remodeling upon stress. This review focuses on three Chromaffin Cell incontrovertible actors, the cholinergic nicotinic receptors and the voltage-dependent T-type Ca^2+ channels that are directly involved in Ca^2+-dependent events controlling catecholamine secretion and electrical activity, and the gap junctional communication involved in the modulation of catecholamine secretion. We show here that these three actors react differently to various stressors, sometimes independently, sometimes in concert or in opposition.
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functional Chromaffin Cell plasticity in response to stress focus on nicotinic gap junction and voltage gated ca2 channels
Journal of Molecular Neuroscience, 2012Co-Authors: Nathalie C Guerineau, Michel G Desarmenien, Valentina Carabelli, Emilio CarboneAbstract:An increase in circulating catecholamines constitutes one of the mechanisms whereby human body responds to stress. In response to chronic stressful situations, the adrenal medullary tissue exhibits crucial morphological and functional changes that are consistent with an improvement of Chromaffin Cell stimulus–secretion coupling efficiency. Stimulus–secretion coupling encompasses multiple intraCellular (Chromaffin Cell excitability, Ca2+ signaling, exocytosis, endocytosis) and interCellular pathways (splanchnic nerve-mediated synaptic transmission, paracrine and endocrine communication, gap junctional coupling), each of them being potentially subjected to functional remodeling upon stress. This review focuses on three Chromaffin Cell incontrovertible actors, the cholinergic nicotinic receptors and the voltage-dependent T-type Ca2+ channels that are directly involved in Ca2+-dependent events controlling catecholamine secretion and electrical activity, and the gap junctional communication involved in the modulation of catecholamine secretion. We show here that these three actors react differently to various stressors, sometimes independently, sometimes in concert or in opposition.
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Revisiting the Stimulus-Secretion Coupling in the Adrenal Medulla: Role of Gap Junction-Mediated InterCellular Communication
Molecular Neurobiology, 2009Co-Authors: Claude Colomer, Michel G Desarmenien, Nathalie C GuerineauAbstract:The current view of stimulation-secretion coupling in adrenal neuroendocrine Chromaffin Cells holds that catecholamines are released upon transsynaptic sympathetic stimulation mediated by acetylcholine released from the splanchnic nerve terminals. However, this traditional vertical scheme would merit to be revisited in the light of recent data. Although electrical discharges invading the splanchnic nerve endings are the major physiological stimulus to trigger catecholamine release in vivo, growing evidence indicates that interCellular Chromaffin Cell communication mediated by gap junctions represents an additional route by which biological signals (electrical activity, changes in intraCellular Ca^2+ concentration,…) propagate between adjacent Cells and trigger subsequent catecholamine exocytosis. Accordingly, it has been proposed that gap junctional communication efficiently helps synapses to lead Chromaffin Cell function and, in particular, hormone secretion. The experimental clues supporting this hypothesis are presented and discussed with regards to both interaction with the excitatory cholinergic synaptic transmission and physiopathology of the adrenal medulla.
Lee E. Eiden - One of the best experts on this subject based on the ideXlab platform.
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pacap signaling in stress insights from the Chromaffin Cell
Pflügers Archiv: European Journal of Physiology, 2018Co-Authors: Lee E. Eiden, Limei Zhang, Andrew C Emery, Corey B SmithAbstract:Pituitary adenylate cyclase-activating polypeptide (PACAP) was first identified in hypothalamus, based on its ability to elevate cyclic AMP in the anterior pituitary. PACAP has been identified as the adrenomedullary neurotransmitter in stress through a combination of ex vivo, in vivo, and in Cellula experiments over the past two decades. PACAP causes catecholamine secretion, and activation of catecholamine biosynthetic enzymes, during episodes of stress in mammals. Features of PACAP signaling allowing stress transduction at the splanchnicoadrenomedullary synapse have yielded insights into the contrasting roles of acetylcholine's and PACAP's actions as first messengers at the Chromaffin Cell, via differential release at low and high rates of splanchnic nerve firing, and differential signaling pathway engagement leading to catecholamine secretion and Chromaffin Cell gene transcription. Secretion stimulated by PACAP, via calcium influx independent of action potential generation, is under active investigation in several laboratories both at the Chromaffin Cell and within autonomic ganglia of both the parasympathetic and sympathetic nervous systems. PACAP is a neurotransmitter important in stress transduction in the central nervous system as well, and is found at stress-transduction nuclei in brain including the paraventricular nucleus of hypothalamus, the amygdala and extended amygdalar nuclei, and the prefrontal cortex. The current status of PACAP as a master regulator of stress signaling in the nervous system derives fundamentally from the establishment of its role as the splanchnicoadrenomedullary transmitter in stress. Experimental elucidation of PACAP action at this synapse remains at the forefront of understanding PACAP's role in stress signaling throughout the nervous system.
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impact of chromogranin a deficiency on catecholamine storage catecholamine granule morphology and Chromaffin Cell energy metabolism in vivo
Cell and Tissue Research, 2016Co-Authors: Teresa Pasqua, Lee E. Eiden, Sumana Mahata, Gautam Bandyopadhyay, Angshuman Biswas, Guy A Perkins, Amiya P Sinhahikim, David GoldsteinAbstract: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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commentary on chapters clinical and developmental aspects and stress responses of the adrenal medulla
Cellular and Molecular Neurobiology, 2010Co-Authors: Lee E. EidenAbstract:The division of the contributions to this volume into Chromogranins, Ion Channels, Secretion Mechanisms, Clinical and Developmental Aspects, and Stress Responses of the Adrenal Medulla is somewhat arbitrary: there is clearly much overlap among these domains of Chromaffin Cell research. This commentary covers both Clinical/ Developmental, and Stress Responses together, mainly to emphasize this overlap, and the translational importance of these two aspects of the Chromaffin Cell as a stress transducer. Genetics, development and stress were three topics of particular clinical relevance that were developed in depth through contributions presented at the 15th International Symposium for Chromaffin Cell Biology. The genetics of the Chromaffin Cell in normal physiology and disease were highlighted by contributions focusing on markers of Chromaffin Cell origin relevant to cancer including pheochromocytoma, and on catecholaminergic markers for hypertension and other cardiovascular diseases. Colon, pancreas, prostate and lung outrank the adrenal medulla as organs of medical concern in human cancer. Although pheochromocytoma, or cancer of adrenomedullary origin is rare, it is an important subject of study for several reasons. First, it arises from a limited and distinct set of Cell types, and therefore is an attractive model for etiology of proliferative disease. Second, pheochromocytoma can be either metastatic, malignant or benign, and therefore can be used to search for markers to make this clinically crucial diagnosis. Murthy et al. propose carboxypeptidase E (CPE), the enkephalin prohormone processing enzyme first characterized in bovine Chromaffin granules in 1982 (Hook et al., Nature 295:341–342, 1982), as such a marker. Meta-analysis of microarray expression data sets in the Gene Expression Omnibus (GEO) allowed Murthy and colleagues to identify CPE as a transcript frequently represented in the transcriptomes of metastatic cancers of both endocrine and epithelial origin. Thus, cervical, colorectal, renal, and bone (Ewing sarcoma), astrocytic, and oligodendroglial tumors or Cells express higher levels of CPE mRNA than their non-cancerous Cells and tissues of origin: in fact most of the corresponding Cells of origin do not have appreciable concentrations of CPE. Lung, pituitary and pheochromocytoma tissue (i.e. neuroendocrine tumors) express higher CPE levels than their tissues of origin. Most significantly, metastatic pheochromocytoma expresses significantly higher CPE mRNA than benign. Should CPE prove a reliable prognostic marker for malignancy in pheochromocytoma and other neuroendocrine cancers, and perhaps even in non-endocrine cancers, its potential for translation to standard clinical practice would be high. Thouennon and Anouar report on expression of neuropeptides in pheochromocytoma that may be involved in trophic, proliferative and angiogenic paracrine/autocrine actions contributing to tumor growth. A strong correlation between NPY and PACAP expression was documented in 25 pheochromocytomas, and between RDC1, the adrenomedullin receptor, and VEGF, with angiogenic activity. These authors review the evidence for concerted expression This is a commentary to articles doi:10.1007/s10571-010-9535-7 10.1007/s10571-010-9567-z, 10.1007/s10571-010-9571-3, 10.1007/s10571-010-9578-9, 10.1007/s10571-010-9575-z, 10.1007/s10571-010-9582-0, 10.1007/s10571-010-9583-z, 10.1007/s10571-010-9592-y, 10.1007/s10571-010-9593-x, 10.1007/s10571-010-9594-9, 10.1007/s10571-010-9600-2, 10.1007/s10571-010-9606-9, 10.1007/s10571-010-9620-y.
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proceedings of the 15th international symposium on Chromaffin Cell biology the Chromaffin Cell as a stress transducer
Cellular and Molecular Neurobiology, 2010Co-Authors: Arturo Hernandezcruz, Lee E. EidenAbstract:It is a great pleasure to present to a larger audience of neurobiologists the Proceedings of the 15th International Symposium on Chromaffin Cell Biology as a Special Issue of Cellular and Molecular Neurobiology. First, a word about the goals of the International Symposia on Chromaffin Cell Biology (ISCCB), and the meeting of which this volume represents the proceedings, and then a brief comment about the organization of this volume itself. The goal of the ISCCB is to provide a forum for the discussion of original high quality research in neuroscience using mainly, but not exclusively, Chromaffin Cells as a biological model. The meeting also provides an opportunity to exchange ideas, promote collaboration between laboratories with complementary methodologies, foster scientific strategies, and especially to bring together senior and junior neuroscientists for a protracted period of time making ‘non-hierarchical’ scientific conversation leading to new ideas and challenging of old ones possible and even inevitable. The 15th edition of the ISCCB was held in the Hyatt Regency Hotel in Merida city, Yucatan, Mexico, 12–16th, Nov 2009. The event was announced widely through the Symposium web page (http://www.ChromaffinCell.org/merida.html), at the Annual Meetings of the Mexican Physiological Society and the Society for Neuroscience. It was also announced at the IBRO, IUBMB and ISN web pages. The participation of young scientists has always been a priority of these Symposia. Thus, for the 2009 meeting, funds were allocated to cover registration and lodging expenses of 27 young scientists. Partial travel aid was provided for four of them. Funds granted by the IUBMB, IBRO, ISN and the National University of Mexico (UNAM) to support this Symposium were used largely to defray the costs of housing and meals of young participants. The total attendance of the 15th ISCCBs was 115 scientists from 22 countries from Europe, Asia, North and South America. More than 40 participants were young scientists. The names of the participants can be found at the ISCCB website (http://www.ChromaffinCell.org/merida.html) where pdf’s of published research and reviews and announcements of future meetings and Chromaffin Cell-related information is also available. For the first time, the ISCCB took place in Mexico. This provided the opportunity for researchers from North America, as well as Central and South America to participate to the Symposium and meet well established neuroscientists from all over the world to exchange ideas and perspectives. An unprecedented number of talks (63 talks in 14 scientific sessions, four plenary lectures, two workshops and one inaugural lecture) were offered throughout the Symposium. In addition, 44 posters were on display during the meeting and time was set aside for their discussion in poster viewing sessions. After the meeting was over, the organizer and members of the Advisory Board were contacted by a number of participants who indicated that the 15th ISCCB represented a highlight in our field and that progress in Chromaffin Cell Biology reported at the meeting was of sufficient interest and impact to justify sharing the proceedings of the meeting with a wider neurobiological and neuroendocrine audience. For this purpose, Lee Eiden, on behalf of the ISCCB Advisory Board, contacted the editor of Cellular and Molecular Neurobiology, Dr. Juan Saavedra, who graciously proposed that a Special Issue of the Journal could be dedicated to the Proceedings. Lee Eiden and Arturo Hernandez-Cruz, organizer of the 15th ISCCB, then accepted the responsibility for actualizing this project. Participation in preparing manuscripts of the meeting’s proceedings was rapid and comprehensive. This volume represents Original Research Contributions (presentation of original results in standard journal format with Materials and Methods, Results and Discussion, of which there are ten), Reviews (comprehensive review of the subject informed by the perspective of the individual participant, of which there are 14), and Meeting Proceedings (in review format, but including the collective contributions, both published and in preparation, of the presenting laboratory and its collaborators on a specific research focus, just as occurred at the meeting itself, of which there are 17). The formats of these contributions represent more than anything else the cyclic nature of research in this as in any field, with some areas ripe for summary and review, and others representing new avenues in which further investigation is anticipated. The Special Issue is divided into five chapters that correspond roughly to the structure of the meeting itself. These are Chromogranins, Ion Channels, Secretion Mechanisms, Stress Response Signaling and Clinical and Developmental Aspects. Each section is preceded by a commentary that attempts to identify some of the themes of Chromaffin Cell biology that are novel, and represent a unique contribution of Chromaffin Cell research to wider aspects of neurobiology. The co-editors are grateful to have had the opportunity and the privilege to recapture and share the excitement of the 15th ISCCB with the readership of Cellular and Molecular Neurobiology.
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Computing the Chromaffin Cell
Annals of the New York Academy of Sciences, 2002Co-Authors: Lee E. Eiden, Michael D. HirschAbstract:Abstract: Exocytosis, stimulus-secretion coupling, real-time measurements of neurosecretion, and stimulus-secretion-synthesis coupling (stimulus-transcription coupling) were all initially proposed and verified in the Chromaffin Cell. Detailed analysis of the molecules and pathways responsible for secretion and transsynaptic regulation of gene expression patterns in neuroendoccrine Cells have been very fruitfully explored in Chromaffin Cells and the related PC12 pheochromocytoma Cell line, using modern molecular biologcal, Cellular imaging, and expression profiling techniques. The time is clearly at hand for a concerted bioinformatics approach to acquiring and synthesizing electrophysiological, biochemical, and proteomic/genomic data on the Chromaffin Cell. Accelerating this process will fully realize the unique attributes of the Chromaffin Cell as a homogeneous, accessible, fully functional model of the posttmitotic neuroendocrine Cell.
Antonio G Garcia - One of the best experts on this subject based on the ideXlab platform.
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mitochondria and Chromaffin Cell function
Pflügers Archiv: European Journal of Physiology, 2012Co-Authors: Javier Garciasancho, Antonio M G De Diego, Antonio G GarciaAbstract:Chromaffin Cells are an exCellent model for stimulus–secretion coupling. Ca2+ entry through plasma membrane voltage-operated Ca2+ channels (VOCC) is the trigger for secretion, but the intraCellular organelles contribute subtle nuances to the Ca2+ signal. The endoplasmic reticulum amplifies the cytosolic Ca2+ ([Ca2+]C) signal by Ca2+-induced Ca2+ release (CICR) and helps generation of microdomains with high [Ca2+]C (HCMD) at the subplasmalemmal region. These HCMD induce exocytosis of the docked secretory vesicles. Mitochondria close to VOCC take up large amounts of Ca2+ from HCMD and stop progression of the Ca2+ wave towards the Cell core. On the other hand, the increase of [Ca2+] at the mitochondrial matrix stimulates respiration and tunes energy production to the increased needs of the exocytic activity. At the end of stimulation, [Ca2+]C decreases rapidly and mitochondria release the Ca2+ accumulated in the matrix through the Na+/Ca2+ exchanger. VOCC, CICR sites and nearby mitochondria form functional triads that co-localize at the subplasmalemmal area, where secretory vesicles wait ready for exocytosis. These triads optimize stimulus–secretion coupling while avoiding propagation of the Ca2+ signal to the Cell core. Perturbation of their functioning in neurons may contribute to the genesis of excitotoxicity, ageing mental retardation and/or neurodegenerative disorders.
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mitochondrial na ca2 exchanger blocker cgp37157 protects against Chromaffin Cell death elicited by veratridine
Journal of Pharmacology and Experimental Therapeutics, 2009Co-Authors: Santos M Nicolau, Antonio M G De Diego, Lorena Cortes, Javier Egea, Jose C Gonzalez, Marta Mosquera, Manuela G Lopez, Jesus M Hernandezguijo, Antonio G GarciaAbstract:Mitochondrial calcium (Ca 2+ ) dyshomeostasis constitutes a critical step in the metabolic crossroads leading to Cell death. Therefore, we have studied here whether 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3 H )-one (CGP37157; CGP), a blocker of the mitochondrial Na + /Ca 2+ -exchanger (mNCX), protects against veratridine-elicited Chromaffin Cell death, a model suitable to study Cell death associated with Ca 2+ overload. Veratridine produced a concentration-dependent Cell death, measured as lactate dehydrogenase released into the medium after a 24-h incubation period. CGP rescued Cells from veratridine-elicited death in a concentration-dependent manner; its EC 50 was approximately 10 μM, and 20 to 30 μM caused near 100% cytoprotection. If preincubated for 30 min and washed out for 3 min before adding veratridine, CGP still afforded significant cytoprotection. At 30 μM, CGP blocked the veratridine-elicited free radical production, mitochondrial depolarization, and cytochrome c release. At this concentration, CGP also inhibited the Na + and Ca 2+ currents by 50 to 60% and the veratridine-elicited oscillations of cytosolic Ca 2+ . This drastic cytoprotective effect of CGP could be explained in part through its regulatory actions on the mNCX.
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Contractile proteins in Chromaffin Cells.
Progress in Brain Research, 2008Co-Authors: Marie-france Bader, Antonio G Garcia, Jaroslava Ciesielski-treska, D Thiersé, Dominique AunisAbstract:Publisher Summary Neurons and Chromaffin Cells share a common embryological origin, the neural crest. The adrenal Chromaffin Cell is a modified post-ganglionic sympathetic ganglion Cell and releases its noradrenergic and adrenergic neurotransmitters into the blood stream, where they act as hormones. On a Cell biology basis, the Chromaffin Cells should be regarded as the relatives of the neurons on the basis of their structure, function, metabolism and origin. According to criteria proposed by Fujita, the Chromaffin Cell is a typical paraneuron. Because of experimental ease, and because of the homogenous population of adrenal paraneurons, the morphology, biochemistry, physiology, pharmacology and pathology of these neural elements have been extensively studied; many important biological concepts have been developed from studies on the adrenal medulla, and extended and extrapolated to peripheric and central neurons. The catecholamines of the adrenal medulla are stored in Chromaffin granules and, upon stimulation by acetylcholine liberated from endings of splanchnic nerve derivations, the content of the granule is released to the exterior of the Cell. The secretion mechanism occurs by exocytosis in which the secretory stimulus first causes the storage granule to fuse with the surface Cell membrane, the fused membrane then opens to the Cell exterior and through this opening the granule content is extruded from the Cell. The similarities between stimulus-secretion coupling and stimulus-contraction coupling in muscle suggest that contractile proteins could play a role in release mechanism.
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depolarization preconditioning produces cytoprotection against veratridine induced Chromaffin Cell death
European Journal of Pharmacology, 2006Co-Authors: Camilo Madariaga Orozco, Antonio G Garcia, Jesus M Hernandezguijo, Mercedes Villarroya, Antonio M Garciadediego, Esperanza Arias, Manuela G LopezAbstract:Abstract The hypothesis that K+ channels and Cell depolarization are involved in neuronal death and neuroprotection was tested in bovine Chromaffin Cells subjected to two treatment periods: the first period (preconditioning period) lasted 6 to 48 h and consisted of treatment with high K+ solutions or with tetraethylammonium (TEA), a K+ channel blocker; the second period consisted of incubation with veratridine for 24 h, to cause Cell damage. Preconditioning with high K+ (20–80 mM) or TEA (10–30 mM) for 24 h caused 20–60% cytoprotection against veratridine-induced Cell death in bovine Chromaffin Cells. The absence of Ca2+ ions during the first 9 h of an 18-h preconditioning period abolished the cytoprotection. Preconditioning with K+ or TEA increased by 2.5-fold the expression of brain-derived neurotrophic factor and by nearly 2-fold the expression of the antiapoptotic protein Bcl-2. However, preconditioning did not modify the veratridine-evoked Ca2+ signal. High K+ shifted the Em by about 10 mV and TEA evoked a transient burst of action potentials superimposed on a sustained depolarization. We conclude that preconditioning may protect Chromaffin Cells from death by blocking K+ channels that depolarize the Cell and cause a cytosolic Ca2+ signal, leading to enhanced expression of BDNF and Bcl-2.
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A twenty-year trip through the Chromaffin Cell.
Annals of the New York Academy of Sciences, 2002Co-Authors: Antonio G GarciaAbstract:: Described here is the origin of a fruitful, long-lasting, and friendly international group of scientists whose main interests are Chromaffin Cells and exocytosis. Meetings have been held every two years in different countries of Europe and North America, and in Japan, Australia, and Israel. We have no formal society or written rules, and our intention is good science and friendship. The first of our International Symposia on Chromaffin Cell Biology (ISCCB-1) was held in Ibiza (Spain) in 1982, and the most recent (ISCCB-11) was held in San Diego (USA) in 2001. These symposia are attended by 100-150 scientists from most European countries, Japan, Israel, the United States, Canada, South America, and Australia. The interest in the Chromaffin Cell as a model for studying basic mechanisms of calcium signaling, Cell-Cell communication, exocytosis, and membrane and vesicle trafficking has been wide; I predict that this interest will grow in the coming years.
Emilio Carbone - One of the best experts on this subject based on the ideXlab platform.
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Functional Chromaffin Cell Plasticity in Response to Stress: Focus on Nicotinic, Gap Junction, and Voltage-Gated Ca^2+ Channels
Journal of Molecular Neuroscience, 2012Co-Authors: Nathalie C Guerineau, Michel G Desarmenien, Valentina Carabelli, Emilio CarboneAbstract:An increase in circulating catecholamines constitutes one of the mechanisms whereby human body responds to stress. In response to chronic stressful situations, the adrenal medullary tissue exhibits crucial morphological and functional changes that are consistent with an improvement of Chromaffin Cell stimulus–secretion coupling efficiency. Stimulus–secretion coupling encompasses multiple intraCellular (Chromaffin Cell excitability, Ca^2+ signaling, exocytosis, endocytosis) and interCellular pathways (splanchnic nerve-mediated synaptic transmission, paracrine and endocrine communication, gap junctional coupling), each of them being potentially subjected to functional remodeling upon stress. This review focuses on three Chromaffin Cell incontrovertible actors, the cholinergic nicotinic receptors and the voltage-dependent T-type Ca^2+ channels that are directly involved in Ca^2+-dependent events controlling catecholamine secretion and electrical activity, and the gap junctional communication involved in the modulation of catecholamine secretion. We show here that these three actors react differently to various stressors, sometimes independently, sometimes in concert or in opposition.
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functional Chromaffin Cell plasticity in response to stress focus on nicotinic gap junction and voltage gated ca2 channels
Journal of Molecular Neuroscience, 2012Co-Authors: Nathalie C Guerineau, Michel G Desarmenien, Valentina Carabelli, Emilio CarboneAbstract:An increase in circulating catecholamines constitutes one of the mechanisms whereby human body responds to stress. In response to chronic stressful situations, the adrenal medullary tissue exhibits crucial morphological and functional changes that are consistent with an improvement of Chromaffin Cell stimulus–secretion coupling efficiency. Stimulus–secretion coupling encompasses multiple intraCellular (Chromaffin Cell excitability, Ca2+ signaling, exocytosis, endocytosis) and interCellular pathways (splanchnic nerve-mediated synaptic transmission, paracrine and endocrine communication, gap junctional coupling), each of them being potentially subjected to functional remodeling upon stress. This review focuses on three Chromaffin Cell incontrovertible actors, the cholinergic nicotinic receptors and the voltage-dependent T-type Ca2+ channels that are directly involved in Ca2+-dependent events controlling catecholamine secretion and electrical activity, and the gap junctional communication involved in the modulation of catecholamine secretion. We show here that these three actors react differently to various stressors, sometimes independently, sometimes in concert or in opposition.