scholarly journals The odorant metabolizing enzyme UGT2A1: Immunolocalization and impact of the modulation of its activity on the olfactory response

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0249029
Author(s):  
Fabrice Neiers ◽  
David Jarriault ◽  
Franck Menetrier ◽  
Loïc Briand ◽  
Jean-Marie Heydel
Keyword(s):  
Plasma Membrane ◽  
Sensory Neurons ◽  
Olfactory Receptors ◽  
Large Family ◽  
Apical Part ◽  
Electronic Microscopy ◽  
Metabolizing Enzymes ◽  
Sustentacular Cells ◽  
Udp Glucuronosyltransferase ◽  
Metabolizing Enzyme

Odorant metabolizing enzymes (OMEs) are expressed in the olfactory epithelium (OE) where they play a significant role in the peripheral olfactory process by catalyzing the fast biotransformation of odorants leading either to their elimination or to the synthesis of new odorant stimuli. The large family of OMEs gathers different classes which interact with a myriad of odorants alike and complementary to olfactory receptors. Thus, it is necessary to increase our knowledge on OMEs to better understand their function in the physiological process of olfaction. This study focused on a major olfactory UDP-glucuronosyltransferase (UGT): UGT2A1. Immunohistochemistry and immunogold electronic microscopy allowed to localize its expression in the apical part of the sustentacular cells and originally at the plasma membrane of the olfactory cilia of the olfactory sensory neurons, both locations in close vicinity with olfactory receptors. Moreover, using electroolfactogram, we showed that a treatment of the OE with beta-glucuronidase, an enzyme which counterbalance the UGTs activity, increased the response to eugenol which is a strong odorant UGT substrate. Altogether, the results supported the function of the olfactory UGTs in the vertebrate olfactory perireceptor process.

SARS-CoV-2 infection causes transient olfactory dysfunction in mice

2020 ◽  
Author(s):  
Qing Ye ◽  
Jia Zhou ◽  
Guan Yang ◽  
Rui-Ting Li ◽  
Qi He ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Olfactory Receptors ◽  
Causal Link ◽  
Olfactory Dysfunction ◽  
Immune Cell Infiltration ◽  
Physiological Basis ◽  
Intranasal Inoculation ◽  
Sustentacular Cells

AbstractOlfactory dysfunction caused by SARS-CoV-2 infection represents as one of the most predictive and common symptoms in COVID-19 patients. However, the causal link between SARS-CoV-2 infection and olfactory disorders remains lacking. Herein we demonstrate intranasal inoculation of SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), resulting in transient olfactory dysfunction in humanized ACE2 mice. The sustentacular cells and Bowman’s gland cells in OE were identified as the major targets of SARS-CoV-2 before the invasion into olfactory sensory neurons. Remarkably, SARS-CoV-2 infection triggers cell death and immune cell infiltration, and impairs the uniformity of OE structure. Combined transcriptomic and proteomic analyses reveal the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptors in OE from the infected animals. Overall, our mouse model recapitulates the olfactory dysfunction in COVID-19 patients, and provides critical clues to understand the physiological basis for extrapulmonary manifestations of COVID-19.

scholarly journals Mitochondria and plasma membrane Ca2+-ATPase control presynaptic Ca2+clearance in capsaicin-sensitive rat sensory neurons

2013 ◽  
Vol 591 (10) ◽  
pp. 2443-2462 ◽  
Author(s):  
Leonid P. Shutov ◽  
Man-Su Kim ◽  
Patrick R. Houlihan ◽  
Yuliya V. Medvedeva ◽  
Yuriy M. Usachev
Keyword(s):  
Plasma Membrane ◽  
Sensory Neurons

scholarly journals Sucrose Accumulation and Related Metabolizing Enzyme Activities in Seeded and Induced Parthenocarpic Muskmelons

2001 ◽  
Vol 126 (6) ◽  
pp. 676-680 ◽  
Author(s):  
Yasuyoshi Hayata ◽  
Xin-Xian Li ◽  
Yutaka Osajima
Keyword(s):  
Sucrose Synthase ◽  
Sucrose Phosphate Synthase ◽  
Invertase Activity ◽  
Activity Level ◽  
Sucrose Accumulation ◽  
Metabolizing Enzymes ◽  
Glucose Content ◽  
Seedless Fruit ◽  
Sucrose Metabolizing Enzymes ◽  
Metabolizing Enzyme

To clarify the cause of low sucrose accumulation in seedless `Crest Earl's' netted muskmelon [Cucumis melo L. (Reticulatus Group)] fruit induced by CPPU, the activity level of sucrose metabolizing enzymes was compared between seeded and seedless fruit. CPPU promoted growth of the ovary in both pollinated and nonpollinated flowers until 10 days after anthesis (DAA), and thereafter the growth rate of nonpollinated fruit was lower than in the controls. Sucrose accumulation of seedless fruit remained lower than in seeded fruit, but there was no difference in fructose and glucose content between seeded and seedless fruit. Acid invertase activity declined sharply 20 DAA in seeded and seedless fruit, and was hardly detectable at 35 DAA, when sucrose accumulation began. Neutral invertase (NI) activity in both seeded and seedless fruit decreased from 20 DAA until 35 DAA; thereafter, NI activity in seeded fruit remained relatively constant, with a small but insignificant increase in maturity. Sucrose synthase (SS-c: sucrose cleavage direction) activity in seeded fruit decreased from 20 to 30 DAA, and then increased as fruit matured, while SS-c activity in seedless fruit did not change during development. Sucrose phosphate synthase (SPS) activity in seeded fruit increased from 25 to 30 DAA and remained relatively constant until harvest. SPS activity in seedless fruit declined gradually from 30 to 45 DAA, then remained at a low level. Sucrose synthase (SS-s: sucrose synthesis direction) activity in seeded fruit increased rapidly after 30 DAA, concomitant with sucrose accumulation. In contrast, SS-s activity in seedless fruit increased only slightly after 30 DAA indicating levels of SS-s activity are closely related to sucrose accumulation in parthenocarpic seedless muskmelons. Chemical name used: [1-(2-chloro-4-pyridyl)-3-phenylurea] (CPPU).

Cranial Nerves I and II

2021 ◽  
pp. 115-119
Author(s):  
Kelly D. Flemming ◽  
Eduardo E. Benarroch
Keyword(s):  
Optic Nerve ◽  
Sensory Neurons ◽  
Chloride Channels ◽  
Calcium Influx ◽  
Cranial Nerves ◽  
Sensory Information ◽  
Olfactory Receptors ◽  
Olfactory Nerve ◽  
Afferent Nerve ◽  
Gated Channel

Cranial nerves I (olfactory nerve) and II (optic nerve) are supratentorial, paired cranial nerves. This chapter provides an overview of their anatomy. Cranial nerve I is a special visceral afferent nerve carrying sensory information about odors. Olfactory receptors lie in the nasal cavity. Odorants activate receptors within the cilia of olfactory sensory neurons and trigger the opening of a cyclic nucleotide–gated channel. This channel allows a calcium influx and the opening of calcium-activated chloride channels. Depolarization then occurs.

scholarly journals Severe Acute Respiratory Syndrome Coronavirus 2 Infects and Damages the Mature and Immature Olfactory Sensory Neurons of Hamsters

2020 ◽  
Author(s):  
Anna Jinxia Zhang ◽  
Andrew Chak-Yiu Lee ◽  
Hin Chu ◽  
Jasper Fuk-Woo Chan ◽  
Zhimeng Fan ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Olfactory Bulb ◽  
Sensory Neurons ◽  
Young Patients ◽  
Olfactory Dysfunction ◽  
Olfactory Sensory Neurons ◽  
Specific Class ◽  
Olfactory Neurons ◽  
Viral Antigens ◽  
Sustentacular Cells

Abstract Background Coronavirus disease 2019 (COVID-19) is primarily an acute respiratory tract infection. Distinctively, a substantial proportion of COVID-19 patients develop olfactory dysfunction. Especially in young patients, loss of smell can be the first or only symptom. The roles of inflammatory obstruction of the olfactory clefts, inflammatory cytokines affecting olfactory neuronal function, destruction of olfactory neurons or their supporting cells, and direct invasion of olfactory bulbs in causing olfactory dysfunction are uncertain. Methods We investigated the location for the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the olfactory epithelium (OE) to the olfactory bulb in golden Syrian hamsters. Results After intranasal inoculation with SARS-CoV-2, inflammatory cell infiltration and proinflammatory cytokine/chemokine responses were detected in the nasal turbinate tissues. The responses peaked between 2 and 4 days postinfection, with the highest viral load detected at day 2 postinfection. In addition to the pseudo-columnar ciliated respiratory epithelial cells, SARS-CoV-2 viral antigens were also detected in the mature olfactory sensory neurons labeled by olfactory marker protein, in the less mature olfactory neurons labeled by neuron-specific class III β-tubulin at the more basal position, and in the sustentacular cells, resulting in apoptosis and severe destruction of the OE. During the entire course of infection, SARS-CoV-2 viral antigens were not detected in the olfactory bulb. Conclusions In addition to acute inflammation at the OE, infection of mature and immature olfactory neurons and the supporting sustentacular cells by SARS-CoV-2 may contribute to the unique olfactory dysfunction related to COVID-19, which is not reported with SARS-CoV-2.

Temporal Development of Cyclic Nucleotide-Gated and Ca2+-Activated Cl− Currents in Isolated Mouse Olfactory Sensory Neurons

2007 ◽  
Vol 98 (1) ◽  
pp. 153-160 ◽  
Author(s):  
Anna Boccaccio ◽  
Anna Menini
Keyword(s):  
Sensory Neurons ◽  
Flash Photolysis ◽  
Olfactory Receptors ◽  
Cell Voltage ◽  
Equilibrium Potential ◽  
Olfactory Sensory Neurons ◽  
Second Phase ◽  
Current Response ◽  
Intact Mouse ◽  
Secondary Current

A Ca2+-activated Cl− current constitutes a large part of the transduction current in olfactory sensory neurons. The binding of odorants to olfactory receptors in the cilia produces an increase in cAMP concentration; Ca2+ enters into the cilia through CNG channels and activates a Cl− current. In intact mouse olfactory sensory neurons little is known about the kinetics of the Ca2+-activated Cl− current. Here, we directly activated CNG channels by flash photolysis of caged cAMP or 8-Br-cAMP and measured the current response with the whole cell voltage-clamp technique in mouse neurons. We measured multiphasic currents in the rising phase of the response at −50 mV. The current rising phase became monophasic in the absence of extracellular Ca2+, at +50 mV, or when most of the intracellular Cl− was replaced by gluconate to shift the equilibrium potential for Cl− to −50 mV. These results show that the second phase of the current in mouse intact neurons is attributed to a Cl− current activated by Ca2+, similarly to previous results on isolated frog cilia. The percentage of the total saturating current carried by Cl− was estimated in two ways: 1) by measuring the maximum secondary current and 2) by blocking the Cl− channel with niflumic acid. We estimated that in the presence of 1 mM extracellular Ca2+ and in symmetrical Cl− concentrations the Cl− component can constitute up to 90% of the total current response. These data show how to unravel the CNG and Ca2+-activated Cl− component of the current rising phase.

scholarly journals Painful Nerve Injury Increases Plasma Membrane Ca2+-ATPase Activity in Axotomized Sensory Neurons

2012 ◽  
Vol 8 ◽  
pp. 1744-8069-8-46 ◽  
Author(s):  
Geza Gemes ◽  
Katherine D Oyster ◽  
Bin Pan ◽  
Hsiang-En Wu ◽  
Madhavi Latha Yadav Bangaru ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Atpase Activity ◽  
Nerve Injury ◽  
Sensory Neurons

Mitochondrial Modulation of Ca2+-Induced Ca2+-Release in Rat Sensory Neurons

2006 ◽  
Vol 96 (3) ◽  
pp. 1093-1104 ◽  
Author(s):  
Joshua G. Jackson ◽  
Stanley A. Thayer
Keyword(s):  
Plasma Membrane ◽  
Sensory Neurons ◽  
Oscillation Frequency ◽  
Cyclopiazonic Acid ◽  
Cellular Level ◽  
Dorsal Root Ganglion Neurons ◽  
Whole Cell Patch Clamp ◽  
Carbonyl Cyanide ◽  
Synthase Inhibitor ◽  
Ganglion Neurons

Ca2+-induced Ca2+-release (CICR) from ryanodine-sensitive Ca2+ stores provides a mechanism to amplify and propagate a transient increase in intracellular calcium concentration ([Ca2+]i). A subset of rat dorsal root ganglion neurons in culture exhibited regenerative CICR when sensitized by caffeine. [Ca2+]i oscillated in the maintained presence of 5 mM caffeine and 25 mM K+. Here, CICR oscillations were used to study the complex interplay between Ca2+ regulatory mechanisms at the cellular level. Oscillations depended on Ca2+ uptake and release from the endoplasmic reticulum (ER) and Ca2+ influx across the plasma membrane because cyclopiazonic acid, ryanodine, and removal of extracellular Ca2+ terminated oscillations. Increasing caffeine concentration decreased the threshold for action potential-evoked CICR and increased oscillation frequency. Mitochondria regulated CICR by providing ATP and buffering [Ca2+]i. Treatment with the ATP synthase inhibitor, oligomycin B, decreased oscillation frequency. When ATP concentration was held constant by recording in the whole cell patch-clamp configuration, oligomycin no longer affected oscillation frequency. Aerobically derived ATP modulated CICR by regulating the rate of Ca2+ sequestration by the ER Ca2+ pump. Neither CICR threshold nor Ca2+ clearance by the plasma membrane Ca2+ pump were affected by inhibition of aerobic metabolism. Uncoupling electron transport with carbonyl cyanide p-trifluoromethoxy-phenyl-hydrazone or inhibiting mitochondrial Na+/Ca2+ exchange with CGP37157 revealed that mitochondrial buffering of [Ca2+]i slowed oscillation frequency, decreased spike amplitude, and increased spike width. These findings illustrate the interdependence of energy metabolism and Ca2+ signaling that results from the complex interaction between the mitochondrion and the ER in sensory neurons.

scholarly journals Identification and Gene Expression Analysis of a Large Family of Transmembrane Kinases Related to the Gal/GalNAc Lectin in Entamoeba histolytica

2005 ◽  
Vol 4 (4) ◽  
pp. 722-732 ◽  
Author(s):  
David L. Beck ◽  
Douglas R. Boettner ◽  
Bojan Dragulev ◽  
Kim Ready ◽  
Tomoyoshi Nozaki ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Entamoeba Histolytica ◽  
Tyrosine Kinases ◽  
Large Family ◽  
Kinase Domain ◽  
Phylogenetic Groups ◽  
Significant Similarity ◽  
Dual Specificity ◽  
Extracellular Stimuli ◽  
Molecular Masses

ABSTRACT We identified in the Entamoeba histolytica genome a family of over 80 putative transmembrane kinases (TMKs). The TMK extracellular domains had significant similarity to the intermediate subunit (Igl) of the parasite Gal/GalNAc lectin. The closest homolog to the E. histolytica TMK kinase domain was a cytoplasmic dual-specificity kinase, SplA, from Dictyostelium discoideum. Sequence analysis of the TMK family demonstrated similarities to both serine/threonine and tyrosine kinases. TMK genes from each of six phylogenetic groups were expressed as mRNA in trophozoites, as assessed by spotted oligoarray and real-time PCR assays, suggesting nonredundant functions of the TMK groups for sensing and responding to extracellular stimuli. Additionally, we observed changes in the expression profile of the TMKs in continuous culture. Antisera produced against the conserved kinase domain identified proteins of the expected molecular masses of the expressed TMKs. Confocal microscopy with anti-TMK kinase antibodies revealed a focal distribution of the TMKs on the cytoplasmic face of the trophozoite plasma membrane. We conclude that E. histolytica expresses members of each subgroup of TMKs. The presence of multiple receptor kinases in the plasma membrane offers for the first time a potential explanation of the ability of the parasite to respond to the changing environment of the host.

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