The Experts below are selected from a list of 273 Experts worldwide ranked by ideXlab platform
Kazushige Touhara - One of the best experts on this subject based on the ideXlab platform.
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origin and evolution of the gene family of proteinaceous pheromones the Exocrine Gland secreting peptides in rodents
Molecular Biology and Evolution, 2021Co-Authors: Yoshihito Niimura, Mai Tsunoda, Sari Kato, Ken Murata, Taichi Yanagawa, Shunta Suzuki, Kazushige TouharaAbstract:The Exocrine-Gland secreting peptide (ESP)gene family encodes proteinaceous pheromones that are recognized by the vomeronasal organ in mice. For example, ESP1 is a male pheromone secreted in tear fluid that regulates socio-sexual behavior, and ESP22 is a juvenile pheromone that suppresses adult sexual behavior. The family consists of multiple genes and has been identified only in mouse and rat genomes. The coding region of a mouse ESP gene is separated into two exons, each encoding signal and mature sequences. Here, we report the origin and evolution of the ESP gene family. ESP genes were found only in the Muridea and Cricetidae families of rodents, suggesting a recent origin of ESP genes in the common ancestor of murids and cricetids. ESP genes show a great diversity in number, length, and sequence among different species as well as mouse strains. Some ESPs in rats and golden hamsters are expressed in the lacrimal Gland and the salivary Gland. We also found that a mature sequence of an ESP gene showed overall sequence similarity to the α-globin gene. The ancestral ESP gene seems to be generated by recombination of a retrotransposed α-globin gene with the signal-encoding exon of the CRISP2 gene located adjacent to the ESP gene cluster. This study provides an intriguing example of molecular tinkering in rapidly evolving species-specific proteinaceous pheromone genes.
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Exocrine Gland secreting peptide 1 is a key chemosensory signal responsible for the bruce effect in mice
Current Biology, 2017Co-Authors: Tatsuya Hattori, Takuya Osakada, Takuto Masaoka, Rumi Ooyama, Nao Horio, Kazutaka Mogi, Miho Nagasawa, Sachiko Hagayamanaka, Kazushige TouharaAbstract:Summary The Bruce effect refers to pregnancy termination in recently pregnant female rodents upon exposure to unfamiliar males [1]. This event occurs in specific combinations of laboratory mouse strains via the vomeronasal system [2, 3]; however, the responsible chemosensory signals have not been fully identified. Here we demonstrate that the male pheromone Exocrine Gland-secreting peptide 1 (ESP1) is one of the key factors that causes pregnancy block. Female mice exhibited high pregnancy failure rates upon encountering males that secreted different levels of ESP1 compared to the mated male. The effect was not observed in mice that lacked the ESP1 receptor, V2Rp5, which is expressed in vomeronasal sensory neurons. Prolactin surges in the blood after mating, which are essential for maintaining luteal function, were suppressed by ESP1 exposure, suggesting that a neuroendocrine mechanism underlies ESP1-mediated pregnancy failure. The single peptide pheromone ESP1 conveys not only maleness to promote female receptivity but also the males' characteristics to facilitate memorization of the mating partner.
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Backbone and side-chain ^1H, ^15N and ^13C assignments of mouse peptide ESP4
Biomolecular NMR Assignments, 2014Co-Authors: Masahiro Taniguchi, Kazushige Touhara, Sosuke Yoshinaga, Sachiko Haga-yamanaka, Hiroaki TerasawaAbstract:A peptide or a small protein released from an Exocrine Gland or in urine is utilized as a chemosignal that elicits social or reproductive behavior in mice. Recently, we identified the male-specific peptide, Exocrine Gland-secreting peptide 1 (ESP1), in mouse tear fluids that enhanced female sexual receptive behavior, and determined the three dimensional structure. ESP1 appears to be a member of multigene family that consists of 38 genes in mice, which we call the ESP family. ESP4, a member of the ESP family, is expressed in various Exocrine Glands, and shows the highest sequence similarity with ESP1. Here, we report the NMR assignments of ESP4 which provides a basis for NMR analyses of this protein. Our results will give insight into structural relationships within the ESP family.
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Murine nonvolatile pheromones: isolation of Exocrine-Gland secreting Peptide 1.
Methods in molecular biology (Clifton N.J.), 2013Co-Authors: Hiroko Kimoto, Kazushige TouharaAbstract:Our search for a substance recognized by the vomeronasal neurons revealed that the extra-orbital lacrimal Gland (ELG) isolated from adult male mice produced the male-specific peptide pheromone Exocrine Gland-secreting peptide 1 (ESP1). The following protocol reveals how ESP1 may be extracted from the ELG, purified using anion-exchange and reverse-phase high-performance liquid chromatography (HPLC), and analyzed by mass spectrometry. This protocol has been specifically designed for the purification of ESP1, but may be modified to isolate a variety of peptides from the Exocrine Glands. Peptides purified in this manner may help further define the molecular mechanisms underlying pheromone communication in the vomeronasal system.
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an unsaturated aliphatic alcohol as a natural ligand for a mouse odorant receptor
Nature Chemical Biology, 2013Co-Authors: Keiichi Yoshikawa, Hiroaki Nakagawa, N Mori, Hidenori Watanabe, Kazushige TouharaAbstract:We report the identification of a physiological receptor-volatile pair in the mouse olfactory system. By activity-guided fractionation of Exocrine Gland extracts and subsequent chemical analysis, (Z)-5-tetradecen-1-ol was identified as a natural ligand for a mouse odorant receptor. (Z)-5-tetradecen-1-ol is excreted into male mouse urine under androgen control and enhances urine attractiveness to female mice. This report is to our knowledge the first to describe natural product-based deorphanization of an odorant receptor.
Conor Murphy - One of the best experts on this subject based on the ideXlab platform.
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profiling micro rna expression in patients with primary sjogrens syndrome contribution to disease pathogenesis
BMC Proceedings, 2015Co-Authors: Rena Alzubaidy, Joan Ni Gabhann, Qistina Pilson, Conor MurphyAbstract:Background Sjogrens syndrome (SS) is a chronic autoimmune disorder, characterised by lymphocytic infiltration resulting in Exocrine Gland destruction and other extra-Glandular manifestations [1]. Currently there is no definitive diagnostic test, and the immuno-pathology is not fully understood. Recently focus has shifted to investigating microRNAs (miRs) in an effort to understand the mechanisms contributing to disease pathogenesis. MiRs are short non-coding RNA sequences, which regulate gene expression posttranscriptionally [2]. Of note, miRs have been identified as key regulators of immune function in a variety of autoimmune conditions [2]. The hypothesis of this project is that alterations in expression of specific miRs which regulate genes relating to inflammation and immunity may play a role in the pathology of the disease.
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Profiling Micro-RNA expression in patients with Primary Sjogrens Syndrome – contribution to disease pathogenesis
BMC Proceedings, 2015Co-Authors: Rena Al-zubaidy, Joan Ni Gabhann, Qistina Pilson, Conor MurphyAbstract:Background Sjogrens syndrome (SS) is a chronic autoimmune disorder, characterised by lymphocytic infiltration resulting in Exocrine Gland destruction and other extra-Glandular manifestations [1]. Currently there is no definitive diagnostic test, and the immuno-pathology is not fully understood. Recently focus has shifted to investigating microRNAs (miRs) in an effort to understand the mechanisms contributing to disease pathogenesis. MiRs are short non-coding RNA sequences, which regulate gene expression posttranscriptionally [2]. Of note, miRs have been identified as key regulators of immune function in a variety of autoimmune conditions [2]. The hypothesis of this project is that alterations in expression of specific miRs which regulate genes relating to inflammation and immunity may play a role in the pathology of the disease.
Yoshikazu Kinoshita - One of the best experts on this subject based on the ideXlab platform.
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Three-dimensional structure of peripheral Exocrine Gland in rat pancreas: reconstruction using transmission electron microscopic examination of serial sections.
Pancreas, 2005Co-Authors: Nobuo Ashizawa, Toshio Sakai, Tsunao Yoneyama, Hiroyuki Naora, Yoshikazu KinoshitaAbstract:The purpose of this study was to elucidate the 3-dimensional structure of the peripheral pancreatic Exocrine Gland. We observed serial sections of rat pancreatic tissue using a transmission electron microscope and traced the intercalated duct lumina, intra-acinar secretory canaliculi, intercalated duct cells or centroacinar cells, and basement membranes of acini onto a transparent sheet. These traced diagrams were reconstructed. The intra-acinar secretory canaliculus had branches but no anastomosis. The intercellular secretory canaliculus was extended from the central lumen through the space between the lateral surfaces of the acinar cells to the acinar base. Furthermore, the cytoplasmic process of each centroacinar cell was extended along the central lumen and connected to an intercalated duct cell; thus, centroacinar cells with the same structure as intercalated duct cells were not isolated from the intercalated duct cells. In this study, we elucidated the normal 3-dimensional structure of the peripheral pancreatic Exocrine Gland. To understand the pathogenesis of chronic pancreatitis, in the future we intend to examine the morphologic changes of pancreatic tissue during the onset and advancement of chronic pancreatitis using animal models.
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Three-dimensional structure of peripheral Exocrine Gland in rat pancreas: reconstruction using transmission electron microscopic examination of serial sections.
Pancreas, 2005Co-Authors: Nobuo Ashizawa, Toshio Sakai, Tsunao Yoneyama, Hiroyuki Naora, Yoshikazu KinoshitaAbstract:OBJECTIVES The purpose of this study was to elucidate the 3-dimensional structure of the peripheral pancreatic Exocrine Gland. METHODS We observed serial sections of rat pancreatic tissue using a transmission electron microscope and traced the intercalated duct lumina, intra-acinar secretory canaliculi, intercalated duct cells or centroacinar cells, and basement membranes of acini onto a transparent sheet. These traced diagrams were reconstructed. RESULTS The intra-acinar secretory canaliculus had branches but no anastomosis. The intercellular secretory canaliculus was extended from the central lumen through the space between the lateral surfaces of the acinar cells to the acinar base. Furthermore, the cytoplasmic process of each centroacinar cell was extended along the central lumen and connected to an intercalated duct cell; thus, centroacinar cells with the same structure as intercalated duct cells were not isolated from the intercalated duct cells. CONCLUSIONS In this study, we elucidated the normal 3-dimensional structure of the peripheral pancreatic Exocrine Gland. To understand the pathogenesis of chronic pancreatitis, in the future we intend to examine the morphologic changes of pancreatic tissue during the onset and advancement of chronic pancreatitis using animal models.
Makoto Tominaga - One of the best experts on this subject based on the ideXlab platform.
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trpv4 heats up ano1 dependent Exocrine Gland fluid secretion
The FASEB Journal, 2017Co-Authors: Sandra Derouiche, Yasunori Takayama, Masataka Murakami, Makoto TominagaAbstract:Several ion channels and transporters regulate fluid secretion in salivary and lacrimal Glands. In salivary Glands, the major anion channel involved in fluid secretion is the calcium-activated chloride channel anoctamin 1 (ANO1). Several members of the transient receptor potential (TRP) channel superfamily regulate ANO1 activity. Here, we report a functional interaction between thermosensitive TRP vanilloid (TRPV)4 and ANO1 in acinar cells isolated from mouse salivary and lacrimal Glands. TRPV4 activation induced chloride currents and shrinkage of acinar cells by increasing intracellular calcium concentrations. The chloride currents evoked by a TRPV4-specific activator (GSK1016790A) were identified as ANO1-mediated currents. Moreover, TRPV4 activation by an inositol 1,4,5-trisphosphate (IP3)-dependent mechanism was found to contribute to the muscarinic pathway of fluid secretion. Muscarinic stimulation of saliva and tear secretion was down-regulated in both TRPV4-deficient mice and in acinar cells treated with a TRPV4-specific antagonist (HC-067047). Furthermore, the temperature dependence of muscarinic salivation was shown to depend mainly on TRPV4. Our results suggest that TRPV4 interacts with IP3 receptors and ANO1 to regulate the muscarinic pathway that mediates salivation and lacrimation.-Derouiche, S., Takayama, Y., Murakami, M., Tominaga, M. TRPV4 heats up ANO1-dependent Exocrine Gland fluid secretion.
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trpv4 heats up ano1 dependent Exocrine Gland fluid secretion
The FASEB Journal, 2017Co-Authors: Sandra Derouiche, Yasunori Takayama, Masataka Murakami, Makoto TominagaAbstract:Several ion channels and transporters regulate fluid secretion in salivary and lacrimal Glands. In salivary Glands, the major anion channel involved in fluid secretion is the calcium-activated chloride channel anoctamin 1 (ANO1). Several members of the transient receptor potential (TRP) channel superfamily regulate ANO1 activity. Here, we report a functional interaction between thermosensitive TRP vanilloid (TRPV)4 and ANO1 in acinar cells isolated from mouse salivary and lacrimal Glands. TRPV4 activation induced chloride currents and shrinkage of acinar cells by increasing intracellular calcium concentrations. The chloride currents evoked by a TRPV4-specific activator (GSK1016790A) were identified as ANO1-mediated currents. Moreover, TRPV4 activation by an inositol 1,4,5-trisphosphate (IP3)-dependent mechanism was found to contribute to the muscarinic pathway of fluid secretion. Muscarinic stimulation of saliva and tear secretion was down-regulated in both TRPV4-deficient mice and in acinar cells treated...
Erik Hviid Larsen - One of the best experts on this subject based on the ideXlab platform.
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patch clamp on the luminal membrane of Exocrine Gland acini from frog skin rana esculenta reveals the presence of cystic fibrosis transmembrane conductance regulator like cl channels activated by cyclic amp
The Journal of General Physiology, 1998Co-Authors: Jakob B Sorensen, Erik Hviid LarsenAbstract:Chloride channels in the luminal membrane of Exocrine Gland acini from frog skin (Rana esculenta) constituted a single homogeneous population. In cell-attached patches, channels activated upon exposure to isoproterenol, forskolin, or dibutyryl-cAMP and isobutyl-1-methyl-xanthine rectified in the outward direction with a conductance of 10.0 ± 0.4 pS for outgoing currents. Channels in stimulated cells reversed at 0 mV applied potential, whereas channels in unstimulated cells reversed at depolarized potentials (28.1 ± 6.7 mV), indicating that Cl− was above electrochemical equilibrium in unstimulated, but not in stimulated, cells. In excised inside-out patches with 25 mM Cl− on the inside, activity of small (8-pS) linear Cl−-selective channels was dependent upon bath ATP (1.5 mM) and increased upon exposure to cAMP-dependent protein kinase. The channels displayed a single substate, located just below 2/3 of the full channel amplitude. Halide selectivity was identified as PBr > PI > PCl from the Goldman equation; however, the conductance sequence when either halide was permeating the channel was GCl > GBr >> GI. In inside-out patches, the channels were blocked reversibly by 5-nitro-2-(3-phenylpropylamino)benzoic acid, glibenclamide, and diphenylamine-2-carboxylic acid, whereas 4,4-diisothiocyanatostilbene-2,2-disulfonic acid blocked channel activity completely and irreversibly. Single-channel kinetics revealed one open state (mean lifetime = 158 ± 72 ms) and two closed states (lifetimes: 12 ± 4 and 224 ± 31 ms, respectively). Power density spectra had a double-Lorentzian form with corner frequencies 0.85 ± 0.11 and 27.9 ± 2.9 Hz, respectively. These channels are considered homologous to the cystic fibrosis transmembrane conductance regulator Cl− channel, which has been localized to the submucosal skin Glands in Xenopus by immunohistochemistry (Engelhardt, J.F., S.S. Smith, E. Allen, J.R. Yankaskas, D.C. Dawson, and J.M. Wilson. 1994. Am. J. Physiol. 267: C491–C500) and, when stimulated by cAMP-dependent phosphorylation, are suggested to function in chloride secretion.
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patch clamp on the luminal membrane of Exocrine Gland acini from frog skin rana esculenta reveals the presence of cystic fibrosis transmembrane conductance regulator like cl channels activated by cyclic amp
The Journal of General Physiology, 1998Co-Authors: Jakob B Sorensen, Erik Hviid LarsenAbstract:Chloride channels in the luminal membrane of Exocrine Gland acini from frog skin (Rana esculenta) constituted a single homogeneous population. In cell-attached patches, channels activated upon exposure to isoproterenol, forskolin, or dibutyryl-cAMP and isobutyl-1-methyl-xanthine rectified in the outward direction with a conductance of 10.0 ± 0.4 pS for outgoing currents. Channels in stimulated cells reversed at 0 mV applied potential, whereas channels in unstimulated cells reversed at depolarized potentials (28.1 ± 6.7 mV), indicating that Cl− was above electrochemical equilibrium in unstimulated, but not in stimulated, cells. In excised inside-out patches with 25 mM Cl− on the inside, activity of small (8-pS) linear Cl−-selective channels was dependent upon bath ATP (1.5 mM) and increased upon exposure to cAMP-dependent protein kinase. The channels displayed a single substate, located just below 2/3 of the full channel amplitude. Halide selectivity was identified as PBr > PI > PCl from the Goldman equation; however, the conductance sequence when either halide was permeating the channel was GCl > GBr >> GI. In inside-out patches, the channels were blocked reversibly by 5-nitro-2-(3-phenylpropylamino)benzoic acid, glibenclamide, and diphenylamine-2-carboxylic acid, whereas 4,4-diisothiocyanatostilbene-2,2-disulfonic acid blocked channel activity completely and irreversibly. Single-channel kinetics revealed one open state (mean lifetime = 158 ± 72 ms) and two closed states (lifetimes: 12 ± 4 and 224 ± 31 ms, respectively). Power density spectra had a double-Lorentzian form with corner frequencies 0.85 ± 0.11 and 27.9 ± 2.9 Hz, respectively. These channels are considered homologous to the cystic fibrosis transmembrane conductance regulator Cl− channel, which has been localized to the submucosal skin Glands in Xenopus by immunohistochemistry (Engelhardt, J.F., S.S. Smith, E. Allen, J.R. Yankaskas, D.C. Dawson, and J.M. Wilson. 1994. Am. J. Physiol. 267: C491–C500) and, when stimulated by cAMP-dependent phosphorylation, are suggested to function in chloride secretion.