The Human Carotid Body

2010 ◽  
Vol 113 (6) ◽  
pp. 1270-1279 ◽  
Author(s):  
Malin Jonsson Fagerlund ◽  
Jessica Kåhlin ◽  
Anette Ebberyd ◽  
Gunnar Schulte ◽  
Souren Mkrtchian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Nicotinic Acetylcholine Receptors ◽  
Carotid Body ◽  
Protein Localization ◽  
Oxygen Sensing ◽  
Radical Neck Dissection ◽  
K Channel ◽  
General Anesthetics ◽  
Anesthetic Drugs

Background Hypoxia is a common cause of adverse events in the postoperative period, where respiratory depression due to residual effects of drugs used in anesthesia is an important underlying factor. General anesthetics and neuromuscular blocking agents reduce the human ventilatory response to hypoxia. Although the carotid body (CB) is the major oxygen sensor in humans, critical oxygen sensing and signaling pathways have been investigated only in animals so far. Thus, the aim of this study was to characterize the expression of key genes and localization of their products involved in the human oxygen sensing and signaling pathways with a focus on receptor systems and ion channels of relevance in anesthesia. Methods Six CBs were removed unilaterally from patients undergoing radical neck dissection. The gene expression and cell-specific protein localization in the CBs were investigated with DNA microarrays, real-time polymerase chain reaction, and immunohistochemistry. Results We found gene expression of the oxygen-sensing pathway, heme oxygenase 2, and the K channels TASK (TWIK-related acid sensitive K channel)-1 and BK (large-conductance potassium channel). In addition, we show the expression of critical receptor subunits such as γ-aminobutyric acid A (α2, β3, and γ2), nicotinic acetylcholine receptors (α3, α7, and β2), purinoceptors (A2A and P2X2), and the dopamine D2 receptor. Conclusions In unique samples of the human CB, we here demonstrate presence of critical proteins in the oxygen-sensing and signaling cascade. Our findings demonstrate similarities to, but also important differences from, established animal models. In addition, our work establishes an essential platform for studying the interaction between anesthetic drugs and human CB chemoreception.

Invited Review: Oxygen sensing during intermittent hypoxia: cellular and molecular mechanisms

2001 ◽  
Vol 90 (5) ◽  
pp. 1986-1994 ◽  
Author(s):  
Nanduri R. Prabhakar
Keyword(s):  
Gene Expression ◽  
Cell Cultures ◽  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Oxygen Sensing ◽  
Regulation Of Gene Expression ◽  
Chronic Intermittent Hypoxia ◽  
Carotid Body Chemoreceptors ◽  
Sustained Hypoxia

To the majority of the population, recurrent episodes of hypoxia are more likely encountered in life than sustained hypoxia. Until recently, much of the information on the long-term effects of intermittent hypoxia has come from studies on human subjects experiencing chronic recurrent apneas. Recent development of animal models of intermittent hypoxia and techniques for exposing cell cultures to alternating cycles of hypoxia have led to new information on the effects of episodic hypoxia on oxygen-sensing mechanisms in the carotid body chemoreceptors and regulation of gene expression. The purpose of this review is to highlight some recent studies on the effects of intermittent hypoxia on oxygen sensing at the carotid bodies and regulation of gene expression. In a rodent model, chronic intermittent hypoxia selectively enhances hypoxic sensitivity of the carotid body chemoreceptors. More interestingly, chronic intermittent hypoxia also induces a novel form of plasticity in the carotid body, leading to long-term facilitation in the sensory discharge. Studies on cell cultures reveal that intermittent hypoxia is more potent in activating activator protein-1 and hypoxia-inducible factor-1 transcription factors than sustained hypoxia. Moreover, some evidence suggests that intermittent hypoxia utilizes intracellular signaling pathways distinct from sustained hypoxia. Reactive oxygen species generated during the reoxygenation phase of intermittent hypoxia might play a key role in the effects of intermittent hypoxia on carotid body function and gene expression. Global gene profile analysis in cell cultures suggests that certain genes are selectively affected by intermittent hypoxia, some upregulated and some downregulated. It is suggested that, in intact animals, coordinated gene regulation of gene expression might be critical for eliciting phenotypic changes in the cardiorespiratory systems in response to intermittent hypoxia. It is hoped that future studies will unravel new mechanisms that are unique to intermittent hypoxia that may lead to a better understanding of the changes in the cardiorespiratory systems and new therapies for diseases associated with chronic recurrent episodes of hypoxia.

scholarly journals Chronic hypoxia changes gene expression profile of primary rat carotid body cells: consequences on the expression of NOS isoforms and ET-1 receptors

2019 ◽  
Vol 51 (4) ◽  
pp. 109-124 ◽  
Author(s):  
Matías Mosqueira ◽  
Rodrigo Iturriaga
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Signaling Pathways ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Carotid Body ◽  
Chronic Hypoxia ◽  
Differentially Expressed ◽  
Network Analyses ◽  
Nos Isoforms

Sustained chronic hypoxia (CH) produces morphological and functional changes in the carotid body (CB). Nitric oxide (NO) and endothelin-1 (ET-1) play a major role as modulators of the CB oxygen chemosensory process. To characterize the effects of CH related to normoxia (Nx) on gene expression, particularly on ET-1 and NO pathways, primary cultures of rat CB cells were exposed to 7 days of CH. Total RNA was extracted, and cDNA-32P was synthesized and hybridized with 1,185 genes printed on a nylon membrane Atlas cDNA Expression Array. Out of 324 differentially expressed genes, 184 genes were upregulated, while 140 genes were downregulated. The cluster annotation and protein network analyses showed that both NO and ET-1 signaling pathways were significantly enriched and key elements of each pathway were differentially expressed. Thus, we assessed the effect of CH at the protein level of nitric oxide synthase (NOS) isoforms and ET-1 receptors. CH induced an increase in the expression of endothelial NOS, inducible NOS, and ETB. During CH, the administration of SNAP, a NO donor, upregulated ETB. Treatment with Tezosentan (ET-1 receptor blocker) during CH upregulated all three NOS isoforms, while the NOS blocker L-NAME induced upregulation of iNOS and ETB and downregulated the protein levels of ETA. These results show that CH for 7 days changed the cultured cell CB gene expression profile, the NO and ET-1 signaling pathways were highly enriched, and these two signaling pathways interfered with the protein expression of each other.

Effect of Propofol on Carotid Body Chemosensitivity and Cholinergic Chemotransduction

2005 ◽  
Vol 102 (1) ◽  
pp. 110-116 ◽  
Author(s):  
Malin M. Jonsson ◽  
Sten G. E. Lindahl ◽  
Lars I. Eriksson
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Carotid Body ◽  
Acetylcholine Receptors ◽  
Carotid Sinus ◽  
Aminobutyric Acid ◽  
Receptor Complex ◽  
Gamma Aminobutyric Acid ◽  
General Anesthetics ◽  
Carotid Sinus Nerve

Background Propofol decreases the acute hypoxic ventilatory response in humans and depresses in vivo carotid body chemosensitivity. The mechanisms behind this impaired oxygen sensing and signaling are not understood. Cholinergic transmission is involved in oxygen signaling, and because general anesthetics such as propofol have affinity to neuronal nicotinic acetylcholine receptors, the authors hypothesized that propofol depresses carotid body chemosensitivity and cholinergic signaling. Methods An isolated rabbit carotid body preparation was used. Chemoreceptor activity was recorded from the whole carotid sinus nerve. The effect of propofol on carotid body chemosensitivity was tested at three different degrees of PO2 reduction. Nicotine-induced chemoreceptor response was evaluated using bolus doses of nicotine given before and after propofol 10-500 microM. The contribution of the gamma-aminobutyric acid A receptor complex was tested by addition of gamma-aminobutyric acid A receptor antagonists. Results Propofol reduced carotid body chemosensitivity; the magnitude of depression was dependent on the reduction in PO2. Furthermore, propofol caused a concentration-dependent (10-500 microM) depression of nicotine-induced chemoreceptor response, with a 50% inhibitory concentration (propofol) of 40 microM. Bicuculline in combination with propofol did not have any additional effect, whereas addition of picrotoxin gave a slightly more pronounced inhibition. Conclusions It is concluded that propofol impairs carotid body chemosensitivity, the magnitude of depression being dependent on the severity of PO2 reduction, and that propofol causes a concentration-dependent block of cholinergic chemotransduction via the carotid sinus nerve, whereas it seems unlikely that an activation of the gamma-aminobutyric acid A receptor complex is involved in this interaction.

Gene expression profiling reveals corticotropin-releasing hormone (CRH) dependent signaling pathways

2005 ◽  
Vol 38 (05) ◽  
Author(s):  
JM Deussing ◽  
C Kühne ◽  
M Panhuysen ◽  
B Pütz ◽  
J Breu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Signaling Pathways ◽  
Expression Profiling ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone

scholarly journals Analysis of the transcriptome of bovine endometrial cells isolated by laser micro-dissection (1): specific signatures of stromal, glandular and luminal epithelial cells

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wiruntita Chankeaw ◽  
Sandra Lignier ◽  
Christophe Richard ◽  
Theodoros Ntallaris ◽  
Mariam Raliou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Localization ◽  
Expression Profiles ◽  
Cell Types ◽  
Molecular Signature ◽  
Receptor Protein ◽  
Specific Gene ◽  
Specific Cell ◽  
Biological Processes ◽  
Endometrial Cells

Abstract Background A number of studies have examined mRNA expression profiles of bovine endometrium at estrus and around the peri-implantation period of pregnancy. However, to date, these studies have been performed on the whole endometrium which is a complex tissue. Consequently, the knowledge of cell-specific gene expression, when analysis performed with whole endometrium, is still weak and obviously limits the relevance of the results of gene expression studies. Thus, the aim of this study was to characterize specific transcriptome of the three main cell-types of the bovine endometrium at day-15 of the estrus cycle. Results In the RNA-Seq analysis, the number of expressed genes detected over 10 transcripts per million was 6622, 7814 and 8242 for LE, GE and ST respectively. ST expressed exclusively 1236 genes while only 551 transcripts were specific to the GE and 330 specific to LE. For ST, over-represented biological processes included many regulation processes and response to stimulus, cell communication and cell adhesion, extracellular matrix organization as well as developmental process. For GE, cilium organization, cilium movement, protein localization to cilium and microtubule-based process were the only four main biological processes enriched. For LE, over-represented biological processes were enzyme linked receptor protein signaling pathway, cell-substrate adhesion and circulatory system process. Conclusion The data show that each endometrial cell-type has a distinct molecular signature and provide a significantly improved overview on the biological process supported by specific cell-types. The most interesting result is that stromal cells express more genes than the two epithelial types and are associated with a greater number of pathways and ontology terms.

scholarly journals Challenges with Methods for Detecting and Studying the Transcription Factor Nuclear Factor Kappa B (NF-κB) in the Central Nervous System

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1335
Author(s):  
Marina Mostafizar ◽  
Claudia Cortes-Pérez ◽  
Wanda Snow ◽  
Jelena Djordjevic ◽  
Aida Adlimoghaddam ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Signaling Pathways ◽  
Quantitative Methods ◽  
Nuclear Factor Kappa B ◽  
Inflammatory Responses ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Regulated Gene Expression ◽  
Transcription Factor Nuclear Factor

The transcription factor nuclear factor kappa B (NF-κB) is highly expressed in almost all types of cells. NF-κB is involved in many complex biological processes, in particular in immunity. The activation of the NF-κB signaling pathways is also associated with cancer, diabetes, neurological disorders and even memory. Hence, NF-κB is a central factor for understanding not only fundamental biological presence but also pathogenesis, and has been the subject of intense study in these contexts. Under healthy physiological conditions, the NF-κB pathway promotes synapse growth and synaptic plasticity in neurons, while in glia, NF-κB signaling can promote pro-inflammatory responses to injury. In addition, NF-κB promotes the maintenance and maturation of B cells regulating gene expression in a majority of diverse signaling pathways. Given this, the protein plays a predominant role in activating the mammalian immune system, where NF-κB-regulated gene expression targets processes of inflammation and host defense. Thus, an understanding of the methodological issues around its detection for localization, quantification, and mechanistic insights should have a broad interest across the molecular neuroscience community. In this review, we summarize the available methods for the proper detection and analysis of NF-κB among various brain tissues, cell types, and subcellular compartments, using both qualitative and quantitative methods. We also summarize the flexibility and performance of these experimental methods for the detection of the protein, accurate quantification in different samples, and the experimental challenges in this regard, as well as suggestions to overcome common challenges.

scholarly journals AB0005 IDENTIFICATION OF KEY GENES AND PATHWAYS FOR PSORIASIS BASED ON GEO DATABASES BY BIOINFORMATICS ANALYSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1037.2-1038
Author(s):  
X. Sun ◽  
S. X. Zhang ◽  
S. Song ◽  
T. Kong ◽  
C. Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathways ◽  
Differentially Expressed Genes ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Shanxi Province ◽  
Receptor Interaction ◽  
Term Therapy ◽  
Pathway Enrichment Analysis ◽  
Key Genes

Background:Psoriasis is an immune-mediated, genetic disease manifesting in the skin or joints or both, and also has a strong genetic predisposition and autoimmune pathogenic traits1. The hallmark of psoriasis is sustained inflammation that leads to uncontrolled keratinocyte proliferation and dysfunctional differentiation. And it’s also a chronic relapsing disease, which often necessitates a long-term therapy2.Objectives:To investigate the molecular mechanisms of psoriasis and find the potential gene targets for diagnosis and treating psoriasis.Methods:Total 334 gene expression data of patients with psoriasis research (GSE13355 GSE14905 and GSE30999) were obtained from the Gene Expression Omnibus database. After data preprocessing and screening of differentially expressed genes (DEGs) by R software. Online toll Metascape3 was used to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs. Interactions of proteins encoded by DEGs were discovered by Protein-protein interaction network (PPI) using STRING online software. Cytoscape software was utilized to visualize PPI and the degree of each DEGs was obtained by analyzing the topological structure of the PPI network.Results:A total of 611 DEGs were found to be differentially expressed in psoriasis. GO analysis revealed that up-regulated DEGs were mostly associated with defense and response to external stimulus while down-regulated DEGs were mostly associated with metabolism and synthesis of lipids. KEGG enrichment analysis suggested they were mainly enriched in IL-17 signaling, Toll-like receptor signaling and PPAR signaling pathways, Cytokine-cytokine receptor interaction and lipid metabolism. In addition, top 9 key genes (CXCL10, OASL, IFIT1, IFIT3, RSAD2, MX1, OAS1, IFI44 and OAS2) were identified through Cytoscape.Conclusion:DEGs of psoriasis may play an essential role in disease development and may be potential pathogeneses of psoriasis.References:[1]Boehncke WH, Schon MP. Psoriasis. Lancet 2015;386(9997):983-94. doi: 10.1016/S0140-6736(14)61909-7 [published Online First: 2015/05/31].[2]Zhang YJ, Sun YZ, Gao XH, et al. Integrated bioinformatic analysis of differentially expressed genes and signaling pathways in plaque psoriasis. Mol Med Rep 2019;20(1):225-35. doi: 10.3892/mmr.2019.10241 [published Online First: 2019/05/23].[3]Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019;10(1):1523. doi: 10.1038/s41467-019-09234-6 [published Online First: 2019/04/05].Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared

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