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  1. Article: Nerve Regeneration and Gait Function Recovery with Implantation of Glucose/Mannose Conduits Using a Rat Model: Efficacy of Glucose/Mannose as a New Neurological Guidance Material.

    Yamamoto, Osamu / Saito, Risa / Ohseki, Yuta / Hoshino, Asami

    Bioengineering (Basel, Switzerland)

    2024  Volume 11, Issue 2

    Abstract: Therapy with clinical nerve guidance conduits often causes functional incompleteness in patients. With the aim of better therapeutic efficacy, nerve regeneration and gait function were investigated in this study using a novel nerve guidance conduit ... ...

    Abstract Therapy with clinical nerve guidance conduits often causes functional incompleteness in patients. With the aim of better therapeutic efficacy, nerve regeneration and gait function were investigated in this study using a novel nerve guidance conduit consisting of glucose/mannose. The glucose/mannose nerve guidance conduits were prepared by filling the conduits with the glucose/mannose aqueous solutions for different kinematic viscosity, which were applied to sciatic nerve defects (6 mm gap) in a rat model. The nerve regeneration effect and the gait function recovery with the fabricated nerve guidance conduits were examined. From the results of the XRD measurement, the glucose/mannose conduits were identified as crystal structures of cellulose type II. Young's modulus and the maximum tensile strength of the crystalline glucose/mannose conduits demonstrated good strength and softness for the human nerve. Above 4 weeks postoperative, macroscopic observation revealed that the nerve was regenerated in the defective area. In various staining results of the nerve tissue removed at 4 weeks postoperative, myelinated nerves contributing to gait function could not be observed in the proximal and distal sites to the central nerve. At 8-12 weeks postoperative, myelinated nerves were found at the proximal and distal sites in hematoxylin/eosin staining. Glia cells were confirmed by phosphotungstic acid-hematoxylin staining. Continuous nerve fibers were observed clearly in the sections of the regenerated nerves towards the longitudinal direction at 12 weeks postoperative. The angle between the metatarsophalangeal joint and the ground plane was approximately 93° in intact rats. At 4 weeks postoperative, walking was not possible, but at 8 weeks postoperative, the rats were able to walk, with an angle of 53°. At 12 weeks postoperative, the angle increased further, reaching 65°, confirming that the rats were able to walk more quickly than at 8 weeks postoperative. These results demonstrated that gait function in rats treated with glucose/mannose nerve guidance conduits was rapidly recovered after 8 weeks postoperative. The glucose/mannose nerve guidance conduit could be applied as a new promising candidate material for peripheral nerve regeneration.
    Language English
    Publishing date 2024-02-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2746191-9
    ISSN 2306-5354
    ISSN 2306-5354
    DOI 10.3390/bioengineering11020157
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Chemosynthetic ethanolamine plasmalogen stimulates gonadotropin secretion from bovine gonadotrophs by acting as a potential GPR61 agonist.

    Kadokawa, Hiroya / Yoshino, Ryunosuke / Saito, Risa / Hirokawa, Takatsugu

    Animal reproduction science

    2022  Volume 241, Page(s) 106992

    Abstract: Brain ethanolamine plasmalogens (EPls) are unique alkenylacyl-glycerophospholipids and the only recognized ligands of G-protein-coupled receptor 61 (GPR61), a newly identified receptor that colocalizes with GnRH receptors on gonadotrophs. As the chemical ...

    Abstract Brain ethanolamine plasmalogens (EPls) are unique alkenylacyl-glycerophospholipids and the only recognized ligands of G-protein-coupled receptor 61 (GPR61), a newly identified receptor that colocalizes with GnRH receptors on gonadotrophs. As the chemical synthesis of EPl is challenging, only one chemosynthetic EPl, 1-(1Z-octadecenyl)- 2-oleoyl-sn-glycero-3-phosphoethanolamine (PLAPE; C18:0-C18:1), is commercially available. Therefore, we tested the hypothesis that PLAPE stimulates gonadotropin secretion from bovine gonadotrophs. We prepared anterior pituitary cells from healthy, post-pubertal heifers, cultured for 3.5 d, and then treated them with increasing concentrations (0, 0.5, 5, 50, or 500 pg/mL) of PLAPE for 5 mi, before either no treatment or GnRH stimulation. After 2 h, medium samples were harvested for FSH and LH assays. PLAPE (5-500 pg/mL) stimulated (P < 0.01) basal FSH and LH secretion, and such stimulation effects were inhibited by a SMAD pathway inhibitor. In the presence of GnRH, PLAPE at 0.5 and 5 pg/mL stimulated FSH and LH secretion (P < 0.01). However, a higher dose of PLAPE (500 pg/mL) suppressed GnRH-induced FSH and LH, and such suppressive effects were inhibited by an ERK pathway inhibitor. PLAPE stimulated gonadotropin secretion in the presence of EPls extracted from the brains of young heifers, but not old cows. Additionally, we performed in silico molecular-docking simulations using the deep-learning algorithm, AlphaFold2. The simulations revealed the presence of three binding sites for PLAPE in the three-dimensional structural model of GPR61. In conclusion, PLAPE stimulated gonadotropin secretion from bovine gonadotrophs and might act as a chemosynthetic agonist of GPR61.
    MeSH term(s) Animals ; Cattle ; Female ; Follicle Stimulating Hormone/metabolism ; Follicle Stimulating Hormone/pharmacology ; Gonadotrophs/metabolism ; Gonadotropin-Releasing Hormone/metabolism ; Gonadotropin-Releasing Hormone/pharmacology ; Plasmalogens/metabolism ; Plasmalogens/pharmacology
    Chemical Substances Plasmalogens ; phosphatidal ethanolamines ; Gonadotropin-Releasing Hormone (33515-09-2) ; Follicle Stimulating Hormone (9002-68-0)
    Language English
    Publishing date 2022-05-13
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 429674-6
    ISSN 1873-2232 ; 0378-4320
    ISSN (online) 1873-2232
    ISSN 0378-4320
    DOI 10.1016/j.anireprosci.2022.106992
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  3. Article: Chemosynthetic ethanolamine plasmalogen stimulates gonadotropin secretion from bovine gonadotrophs by acting as a potential GPR61 agonist

    Kadokawa, Hiroya / Yoshino, Ryunosuke / Saito, Risa / Hirokawa, Takatsugu

    Animal reproduction science. 2022 June, v. 241

    2022  

    Abstract: Brain ethanolamine plasmalogens (EPls) are unique alkenylacyl-glycerophospholipids and the only recognized ligands of G-protein-coupled receptor 61 (GPR61), a newly identified receptor that colocalizes with GnRH receptors on gonadotrophs. As the chemical ...

    Abstract Brain ethanolamine plasmalogens (EPls) are unique alkenylacyl-glycerophospholipids and the only recognized ligands of G-protein-coupled receptor 61 (GPR61), a newly identified receptor that colocalizes with GnRH receptors on gonadotrophs. As the chemical synthesis of EPl is challenging, only one chemosynthetic EPl, 1-(1Z-octadecenyl)− 2-oleoyl-sn-glycero-3-phosphoethanolamine (PLAPE; C18:0-C18:1), is commercially available. Therefore, we tested the hypothesis that PLAPE stimulates gonadotropin secretion from bovine gonadotrophs. We prepared anterior pituitary cells from healthy, post-pubertal heifers, cultured for 3.5 d, and then treated them with increasing concentrations (0, 0.5, 5, 50, or 500 pg/mL) of PLAPE for 5 mi, before either no treatment or GnRH stimulation. After 2 h, medium samples were harvested for FSH and LH assays. PLAPE (5–500 pg/mL) stimulated (P < 0.01) basal FSH and LH secretion, and such stimulation effects were inhibited by a SMAD pathway inhibitor. In the presence of GnRH, PLAPE at 0.5 and 5 pg/mL stimulated FSH and LH secretion (P < 0.01). However, a higher dose of PLAPE (500 pg/mL) suppressed GnRH-induced FSH and LH, and such suppressive effects were inhibited by an ERK pathway inhibitor. PLAPE stimulated gonadotropin secretion in the presence of EPls extracted from the brains of young heifers, but not old cows. Additionally, we performed in silico molecular-docking simulations using the deep-learning algorithm, AlphaFold2. The simulations revealed the presence of three binding sites for PLAPE in the three-dimensional structural model of GPR61. In conclusion, PLAPE stimulated gonadotropin secretion from bovine gonadotrophs and might act as a chemosynthetic agonist of GPR61.
    Keywords G-protein coupled receptors ; agonists ; algorithms ; animal reproduction ; anterior pituitary ; brain ; computer simulation ; ethanolamine ; ligands ; models ; secretion ; synthesis
    Language English
    Dates of publication 2022-06
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 429674-6
    ISSN 1873-2232 ; 0378-4320
    ISSN (online) 1873-2232
    ISSN 0378-4320
    DOI 10.1016/j.anireprosci.2022.106992
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Dynamic changes and importance of plasma concentrations of ether phospholipids, of which the majority are plasmalogens, in postpartum Holstein dairy cows

    Saito, Risa / Kubo, Tomoaki / Wakatsuki, Takuji / Asato, Yuuki / Tanigawa, Tamako / Kotaniguchi, Miyako / Hashimoto, Maki / Kitamura, Shinichi / Kadokawa, Hiroya

    Reproduction, Fertility and Development. 2023, v. 35, no. 12 p.622-639

    2023  

    Abstract: Context: Ethanolamine plasmalogens (EPls) and choline plasmalogens (CPls) are classes of ethanolamine ether phospholipids (ePE) and choline ether phospholipids (ePC), respectively. EPls play crucial roles in maternal and breastfed infant bodies and ... ...

    Abstract Context: Ethanolamine plasmalogens (EPls) and choline plasmalogens (CPls) are classes of ethanolamine ether phospholipids (ePE) and choline ether phospholipids (ePC), respectively. EPls play crucial roles in maternal and breastfed infant bodies and stimulate gonadotropin secretion by gonadotrophs. Aims: To estimate changes in and importance of plasma concentrations of EPls and CPls, utilising newly developed enzymatic fluorometric assays for ePE and ePC in postpartum Holstein cows. Methods: Plasma samples were collected from 3weeks before expected parturition until approximately 8weeks after parturition (16 primiparous and 38 multiparous cows) for analysis. Key results: Plasma concentrations of ePE and ePC, most of which are plasmalogens, declined before and increased after parturition and stabilised near the day of the first postpartum ovulation (1stOV). From weeks 2 to 3 after parturition, third-parity cows exhibited ePE concentrations that were higher than those of other parity cows. The days from parturition to 1stOV correlated with days from parturition to conception. On the day of 1stOV, milk yield correlated with plasma concentration of both ePE and ePC, while ePC concentration correlated negatively with milk fat percentage. At the early luteal phase after 1stOV, plasma ePE concentration correlated with plasma anti-Müllerian hormone concentration (r =0.39, P <0.01), and plasma ePC concentration correlated with plasma follicle-stimulating hormone concentration (r =0.43, P <0.01). Conclusion: The concentrations of ePE and ePC changed dramatically around parturition and 1stOV, and the concentrations correlated with important parameters for milk production and reproduction. Implications: The blood plasmalogen may play important roles in postpartum dairy cows.
    Keywords Holstein ; blood ; breast feeding ; choline ; conception ; ethanolamine ; fluorometry ; follicle-stimulating hormone ; menstrual cycle ; milk fat percentage ; milk yield ; ovulation ; parity (reproduction) ; parturition ; phospholipids ; secretion ; aging ; anti-Müllerian hormone ; choline plasmalogen ; ethanolamine plasmalogens ; first postpartum ovulation ; FSH ; functional lipids ; G protein-coupled receptor 61 ; GPR61 ; LH ; parity ; phospholipase A1 ; postpartum Holstein dairy cows ; ruminant
    Language English
    Size p. 622-639.
    Publishing place CSIRO Publishing
    Document type Article ; Online
    ZDB-ID 1019913-5
    ISSN 1448-5990 ; 1031-3613
    ISSN (online) 1448-5990
    ISSN 1031-3613
    DOI 10.1071/RD23057
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  5. Article ; Online: Spike protein of SARS-CoV-2 suppresses gonadotrophin secretion from bovine anterior pituitaries.

    Abdillah, Dimas Arya / Kereilwe, Onalenna / Ferdousy, Raihana Nasrin / Saito, Risa / Kadokawa, Hiroya

    The Journal of reproduction and development

    2022  Volume 68, Issue 2, Page(s) 152–159

    Abstract: Coronavirus disease (COVID-19), the ongoing global pandemic, is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent evidence shows that the virus utilizes angiotensin-converting enzyme 2 (ACE2) as a spike protein receptor ... ...

    Abstract Coronavirus disease (COVID-19), the ongoing global pandemic, is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent evidence shows that the virus utilizes angiotensin-converting enzyme 2 (ACE2) as a spike protein receptor for entry into target host cells. The bovine ACE2 contains key residues for binding to the spike protein receptor-binding domain. This study evaluated the hypothesis that bovine gonadotroph expresses ACE2, and spike protein suppresses luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion from cultured bovine anterior pituitary (AP) cells. ACE2 mRNA expression and ACE2 protein expression were detected in the bovine AP cells using reverse transcription PCR and western blot analysis. Immunofluorescence microscopy analysis with the anti-ACE2 antibody revealed the co-localization of ACE2 and gonadotropin-releasing hormone (GnRH) receptor on the gonadotroph plasma membrane. Approximately 90% of GnRH receptor-positive cells expressed ACE2, and approximately 46% of ACE2-positive cells expressed the GnRH receptor. We cultured bovine AP cells for 3.5 days and treated them with increasing concentrations (0, 0.07, 0.7, or 7 pM) of recombinant spike protein having both S1 and S2 regions. The spike protein (0.07-7 pM) suppressed both basal and GnRH-induced LH secretion (P < 0.05). Spike protein (0.7-7 pM) suppressed GnRH-induced (P < 0.05), but not basal FSH secretion. In contrast, pre-treatment with ERK 1/2/5 inhibitor (U0126) partially restored the GnRH-induced LH and FSH secretion from the spike protein suppression. Collectively, the results indicate that gonadotrophs express ACE2, a receptor for coronavirus 2 spike protein, which in turn suppresses LH and FSH secretion from AP cells.
    MeSH term(s) Angiotensin-Converting Enzyme 2 ; Animals ; COVID-19 ; Cattle ; Follicle Stimulating Hormone/metabolism ; Luteinizing Hormone/metabolism ; Pituitary Gland, Anterior/metabolism ; Receptors, LHRH/metabolism ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/metabolism
    Chemical Substances Receptors, LHRH ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Luteinizing Hormone (9002-67-9) ; Follicle Stimulating Hormone (9002-68-0) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Language English
    Publishing date 2022-01-27
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2039060-9
    ISSN 1348-4400 ; 0916-8818
    ISSN (online) 1348-4400
    ISSN 0916-8818
    DOI 10.1262/jrd.2021-126
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  6. Article ; Online: Ethanolamine plasmalogens derived from scallops stimulate both follicle-stimulating hormone and luteinizing hormone secretion by bovine gonadotrophs.

    Kadokawa, Hiroya / Kotaniguchi, Miyako / Mawatari, Shiro / Saito, Risa / Fujino, Takehiko / Kitamura, Shinichi

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 16789

    Abstract: Brain ethanolamine plasmalogens (EPls) are the only known ligands of G-protein-coupled receptor 61, a novel receptor that stimulates follicle-stimulating hormone (FSH), but not luteinizing hormone (LH), secretion by bovine gonadotrophs. We hypothesized ... ...

    Abstract Brain ethanolamine plasmalogens (EPls) are the only known ligands of G-protein-coupled receptor 61, a novel receptor that stimulates follicle-stimulating hormone (FSH), but not luteinizing hormone (LH), secretion by bovine gonadotrophs. We hypothesized that the recently developed neuroprotective EPls extracted from scallop (Pecten yessoensis) (scallop EPls) could stimulate FSH secretion by gonadotrophs. To test this hypothesis, bovine gonadotrophs were cultured for 3.5 days and treated with increasing concentrations of scallop EPls. FSH secretion was stimulated by all tested concentrations of scallop EPls (P < 0.05). Surprisingly, LH secretion was stimulated by both 0.5 (P < 0.05) and 5 (P < 0.01) ng/mL of scallop EPls. To clarify the important differences between bovine brain and scallop EPls, we utilized two-dimensional liquid chromatography-mass spectrometry, which revealed 44 peaks, including 10 large peaks. Among them, eight were scallop-specific EPl molecular species, occupying approximately 58% of the total area percentage of scallop EPls. Almost all large peaks contained 4, 5, or 6 unsaturated double bonds in the carbon chain at the sn-2 position of the glycerol backbone. Our results showed that EPls from scallops, lacking pituitary glands, stimulated both FSH and LH secretion by bovine gonadotrophs.
    MeSH term(s) Animals ; Carbon ; Cattle ; Follicle Stimulating Hormone ; Glycerol ; Gonadotrophs/metabolism ; Gonadotropin-Releasing Hormone/metabolism ; Pectinidae/metabolism ; Pituitary Gland/metabolism ; Pituitary Gland, Anterior/metabolism ; Plasmalogens ; Receptors, G-Protein-Coupled
    Chemical Substances Plasmalogens ; Receptors, G-Protein-Coupled ; phosphatidal ethanolamines ; Gonadotropin-Releasing Hormone (33515-09-2) ; Carbon (7440-44-0) ; Follicle Stimulating Hormone (9002-68-0) ; Glycerol (PDC6A3C0OX)
    Language English
    Publishing date 2022-10-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-20794-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Ethanolamine plasmalogens derived from whale brain stimulate both follicle-stimulating hormone and luteinizing hormone secretion by bovine gonadotrophs.

    Saito, Risa / Bando, Takeharu / Kotaniguchi, Miyako / Tamura, Tsutomu / Kuno, Tomoe / Watanabe, Kenji / Mizukami, Yoichi / Kitamura, Shinichi / Kadokawa, Hiroya

    Animal science journal = Nihon chikusan Gakkaiho

    2023  Volume 94, Issue 1, Page(s) e13839

    Abstract: Ethanolamine plasmalogens (EPls) are the only known ligands of a novel receptor, G protein-coupled receptor 61, and bovine brain EPls stimulate follicle-stimulating hormone (FSH) but not luteinizing hormone (LH), secreted by bovine gonadotrophs. We ... ...

    Abstract Ethanolamine plasmalogens (EPls) are the only known ligands of a novel receptor, G protein-coupled receptor 61, and bovine brain EPls stimulate follicle-stimulating hormone (FSH) but not luteinizing hormone (LH), secreted by bovine gonadotrophs. We hypothesized that the brain EPls of whales (Balaenoptera edeni), another Cetartiodactyla with at least twice the lifespan of bovines, could stimulate FSH secretion by gonadotrophs. To test this hypothesis, bovine gonadotrophs (from approximately 2-year-old Japanese Black heifers) were cultured for 3.5 days and treated with increasing concentrations of brain EP1s from whales (approximately 22 years old). FSH and LH secretion was stimulated by all tested concentrations of whale EPls (p < 0.05). To clarify the important differences between bovine and whale EPls, we utilized two-dimensional liquid chromatography-mass spectrometry, which revealed 35 peaks. Among them, we observed significant differences between 12 EPl molecular species. Additionally, we identified differentially expressed genes for enzymes involved in EPl synthesis or degradation in the hypothalamus of young heifers and old cows (approximately 10 years old) as compared to whales (approximately 28 years old) via deep sequencing of the transcriptome. We conclude that whale brains contain unique EPls that stimulate both FSH and LH secretion by bovine gonadotrophs.
    MeSH term(s) Cattle ; Animals ; Female ; Follicle Stimulating Hormone/metabolism ; Gonadotrophs/metabolism ; Whales/metabolism ; Gonadotropin-Releasing Hormone ; Brain/metabolism ; Pituitary Gland, Anterior/metabolism
    Chemical Substances Follicle Stimulating Hormone (9002-68-0) ; phosphatidal ethanolamines ; Gonadotropin-Releasing Hormone (33515-09-2)
    Language English
    Publishing date 2023-05-29
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 2095161-9
    ISSN 1740-0929 ; 1344-3941
    ISSN (online) 1740-0929
    ISSN 1344-3941
    DOI 10.1111/asj.13839
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  8. Article: Dynamic changes and importance of plasma concentrations of ether phospholipids, of which the majority are plasmalogens, in postpartum Holstein dairy cows.

    Saito, Risa / Kubo, Tomoaki / Wakatsuki, Takuji / Asato, Yuuki / Tanigawa, Tamako / Kotaniguchi, Miyako / Hashimoto, Maki / Kitamura, Shinichi / Kadokawa, Hiroya

    Reproduction, fertility, and development

    2023  Volume 35, Issue 12, Page(s) 622–639

    Abstract: Context: Ethanolamine plasmalogens (EPls) and choline plasmalogens (CPls) are classes of ethanolamine ether phospholipids (ePE) and choline ether phospholipids (ePC), respectively. EPls play crucial roles in maternal and breastfed infant bodies and ... ...

    Abstract Context: Ethanolamine plasmalogens (EPls) and choline plasmalogens (CPls) are classes of ethanolamine ether phospholipids (ePE) and choline ether phospholipids (ePC), respectively. EPls play crucial roles in maternal and breastfed infant bodies and stimulate gonadotropin secretion by gonadotrophs.
    Aims: To estimate changes in and importance of plasma concentrations of EPls and CPls, utilising newly developed enzymatic fluorometric assays for ePE and ePC in postpartum Holstein cows.
    Methods: Plasma samples were collected from 3weeks before expected parturition until approximately 8weeks after parturition (16 primiparous and 38 multiparous cows) for analysis.
    Key results: Plasma concentrations of ePE and ePC, most of which are plasmalogens, declined before and increased after parturition and stabilised near the day of the first postpartum ovulation (1stOV). From weeks 2 to 3 after parturition, third-parity cows exhibited ePE concentrations that were higher than those of other parity cows. The days from parturition to 1stOV correlated with days from parturition to conception. On the day of 1stOV, milk yield correlated with plasma concentration of both ePE and ePC, while ePC concentration correlated negatively with milk fat percentage. At the early luteal phase after 1stOV, plasma ePE concentration correlated with plasma anti-Müllerian hormone concentration (r =0.39, P <0.01), and plasma ePC concentration correlated with plasma follicle-stimulating hormone concentration (r =0.43, P <0.01).
    Conclusion: The concentrations of ePE and ePC changed dramatically around parturition and 1stOV, and the concentrations correlated with important parameters for milk production and reproduction.
    Implications: The blood plasmalogen may play important roles in postpartum dairy cows.
    MeSH term(s) Pregnancy ; Female ; Humans ; Cattle ; Animals ; Plasmalogens ; Phospholipid Ethers ; Lactation ; Postpartum Period ; Parturition ; Parity ; Milk
    Chemical Substances Plasmalogens ; Phospholipid Ethers
    Language English
    Publishing date 2023-07-18
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 1019913-5
    ISSN 1448-5990 ; 1031-3613
    ISSN (online) 1448-5990
    ISSN 1031-3613
    DOI 10.1071/RD23057
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  9. Article ; Online: Identification of Functional Domains of CXCL14 Involved in High-Affinity Binding and Intracellular Transport of CpG DNA.

    Iwase, Rina / Naruse, Naoto / Nakagawa, Miho / Saito, Risa / Shigenaga, Akira / Otaka, Akira / Hara, Takahiko / Tanegashima, Kosuke

    Journal of immunology (Baltimore, Md. : 1950)

    2021  Volume 207, Issue 2, Page(s) 459–469

    Abstract: Some CXC chemokines, including CXCL14, transport CpG oligodeoxynucleotides (ODNs) into dendritic cells (DCs), thereby activating TLR9. The molecular basis of this noncanonical function of CXC chemokines is not well understood. In this study, we ... ...

    Abstract Some CXC chemokines, including CXCL14, transport CpG oligodeoxynucleotides (ODNs) into dendritic cells (DCs), thereby activating TLR9. The molecular basis of this noncanonical function of CXC chemokines is not well understood. In this study, we investigated the CpG ODN binding and intracellular transport activities of various CXC chemokines and partial peptides of CXCL14 in mouse bone marrow-derived dendritic cells. CXCL14, CXCL4, and CXCL12 specifically bound CpG ODN, but CXCL12 failed to transport it into cells at low dose. CXCL14 N-terminal peptides 1-47, but not 1-40, was capable of transporting CpG ODN into the cell, resulting in an increase in cytokine production. However, both the 1-47 and 1-40 peptides bound CpG ODN. By contrast, CXCL14 peptides 13-50 did not possess CpG ODN binding capacity or transport activity. The chimeric peptides CXCL12 (1-22)-CXCL14 (13-47) bound CpG ODN but failed to transport it. These results suggest that amino acids 1-12 and 41-47 of CXCL14 are required for binding and intracellular transport of CpG ODN, respectively. We found that an anti-CXCL14 Ab blocked cell-surface binding and internalization of the CpG ODN/CXCL14 complex. On the basis of these findings, we propose that CXCL14 has two functional domains, one involved in DNA recognition and the other in internalization of CXCL14-CpG DNA complex via an unidentified CXCL14 receptor, which together are responsible for eliciting the CXCL14/CpG ODN-mediated TLR9 activation. These domains could play roles in CXCL14-related diseases such as arthritis, obesity-induced diabetes, and various types of carcinoma.
    MeSH term(s) Adjuvants, Immunologic/metabolism ; Animals ; Biological Transport/physiology ; Cell Line ; Cell Membrane/metabolism ; Chemokine CXCL12/metabolism ; Chemokines, CXC/metabolism ; Cytokines/metabolism ; DNA/metabolism ; Mice ; Mice, Inbred C57BL ; Oligodeoxyribonucleotides/metabolism ; RAW 264.7 Cells ; Toll-Like Receptor 9/metabolism
    Chemical Substances Adjuvants, Immunologic ; CPG-oligonucleotide ; CXCL14 protein, mouse ; Chemokine CXCL12 ; Chemokines, CXC ; Cytokines ; Oligodeoxyribonucleotides ; Toll-Like Receptor 9 ; DNA (9007-49-2)
    Language English
    Publishing date 2021-07-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.2100030
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  10. Article ; Online: The current status of robotic surgery for endometrial cancer in Japan.

    Gota, Tomoko / Tomio, Kensuke / Kurose, Taichi / Saito, Risa / Nara, Ryoken / Kin, Sohmi / Hoshiba, Minami / Ogata, Yuri / Nakanishi, Misao / Takamoto, Maya / Sadatsuki, Miyuki / Oishi, Hajime

    Global health & medicine

    2022  Volume 4, Issue 1, Page(s) 21–25

    Abstract: ... The da ... ...

    Abstract The da Vinci
    Language English
    Publishing date 2022-03-15
    Publishing country Japan
    Document type Journal Article ; Review
    ISSN 2434-9194
    ISSN (online) 2434-9194
    DOI 10.35772/ghm.2021.01077
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