The Experts below are selected from a list of 594 Experts worldwide ranked by ideXlab platform

Gerhard Wagner - One of the best experts on this subject based on the ideXlab platform.

  • cytidine monophosphate n acetylneuraminic Acid synthetase enhances invasion of human triple negative breast cancer cells
    OncoTargets and Therapy, 2018
    Co-Authors: Elizabeth Oday, Greg E Idos, Collin Hill, Joan W Chen, Gerhard Wagner
    Abstract:

    Background: Cancer cells have altered bioenergetics, which contributes to their ability to proliferate, survive in unusual microenvironments, and invade other tissues. Changes in glucose metabolism can have pleomorphic effects on tumor cells. Methods: To investigate potential mechanisms responsible for the increased malignancy associated with altered glucose metabolism, we used an unbiased nuclear magnetic resonance spectroscopy screening method to identify glucose metabolites differentially produced in a highly malignant human triple-negative breast cancer (TNBC) cell line (BPLER) and a less malignant isogenic TNBC cell line (HMLER). Results: N-acetylneuraminic Acid (Neu5Ac), the predominant Sialic Acid Derivative in mammalian cells, which forms the terminal sugar on mucinous cell surface glycoproteins, was the major glucose metabolite that differed. Neu5Ac was ~7-fold more abundant in BPLER than HMLER. Loss of Neu5Ac by enzymatic removal or siRNA knockdown of cytidine monophosphate N-acetylneuraminic Acid synthetase (CMAS), which activates cellular Sialic Acids for glycoprotein conjugation, had no significant effect on cell proliferation, but decreased the ability of BPLER to invade through a basement membrane. Conversely, overexpressing CMAS in HMLER increased invasivity. TNBCs in The Cancer Genome Atlas also had significantly more CMAS copy number variations and higher mRNA expression than non-TNBC, which have a better prognosis. CMAS knockdown in BPLER ex vivo blocked xenograft formation in mice. Conclusion: Neu5Ac is selectively highly enriched in aggressive TNBC, and CMAS, the enzyme required for sialylation, may play an important role in TNBC tumor formation and invasivity.

Hokuto Fukumoto - One of the best experts on this subject based on the ideXlab platform.

  • rapid regulation of sialidase activity in response to neural activity and Sialic Acid removal during memory processing in rat hippocampus
    Journal of Biological Chemistry, 2017
    Co-Authors: Akira Minami, Yuuki Horii, Hokuto Fukumoto, Yuko Meguro, Sayaka Ishibashi, Ami Ishii, Mako Shiratori, Saki Sai, Hirotaka Shimizu, Sumika Shimba
    Abstract:

    Sialidase cleaves Sialic Acids on the extracellular cell surface as well as inside the cell and is necessary for normal long-term potentiation (LTP) at mossy fiber-CA3 pyramidal cell synapses and for hippocampus-dependent spatial memory. Here, we investigated in detail the role of sialidase in memory processing. Sialidase activity measured with 4-methylumbelliferyl-α-d-N-acetylneuraminic Acid (4MU-Neu5Ac) or 5-bromo-4-chloroindol-3-yl-α-d-N-acetylneuraminic Acid (X-Neu5Ac) and Fast Red Violet LB was increased by high-K+-induced membrane depolarization. Sialidase activity was also increased by chemical LTP induction with forskolin and activation of BDNF signaling, non-NMDA receptors, or NMDA receptors. The increase in sialidase activity with neural excitation appears to be caused not by secreted sialidase or by an increase in sialidase expression but by a change in the subcellular localization of sialidase. Astrocytes as well as neurons are also involved in the neural activity-dependent increase in sialidase activity. Sialidase activity visualized with a benzothiazolylphenol-based Sialic Acid Derivative (BTP3-Neu5Ac), a highly sensitive histochemical imaging probe for sialidase activity, at the CA3 stratum lucidum of rat acute hippocampal slices was immediately increased in response to LTP-inducible high-frequency stimulation on a time scale of seconds. To obtain direct evidence for Sialic Acid removal on the extracellular cell surface during neural excitation, the extracellular free Sialic Acid level in the hippocampus was monitored using in vivo microdialysis. The free Sialic Acid level was increased by high-K+-induced membrane depolarization. Desialylation also occurred during hippocampus-dependent memory formation in a contextual fear-conditioning paradigm. Our results show that neural activity-dependent desialylation by sialidase may be involved in hippocampal memory processing.

  • Visualization of Sialidase Activity in Mammalian Tissues and Cancer Detection with a Novel Fluorescent Sialidase Substrate
    PLoS ONE, 2014
    Co-Authors: Akira Minami, Tadamune Otsubo, Daisuke Ieno, Kiyoshi Ikeda, Hiroaki Kanazawa, Kosuke Shimizu, Ko Ohata, Tsunehiro Yokochi, Yuuki Horii, Hokuto Fukumoto
    Abstract:

    Sialidase removes Sialic Acid from sialoglycoconjugates and plays crucial roles in many physiological and pathological processes. Various human cancers express an abnormally high level of the plasma membrane-associated sialidase isoform.Visualization of sialidase activity in living mammalian tissues would be useful not only for understanding sialidase functions but also for cancer diagnosis. However, since enzyme activity of mammalian sialidase is remarkably weak compared with that of bacterial and viral sialidases, it has been difficult to detect sialidase activity in mammalian tissues. We synthesized a novel benzothiazolylphenol-based Sialic Acid Derivative (BTP-Neu5Ac) as a fluorescent sialidase substrate. BTP-Neu5Ac can visualize sialidase activities sensitively and selectively in acute rat brain slices. Cancer cells implanted orthotopically in mouse colons and human colon cancers (stages T3-T4) were also clearly detected with BTP-Neu5Ac. The results suggest that BTP-Neu5Ac is useful for histochemical imaging of sialidase activities.

  • Visualization of Sialidase Activity in Mammalian Tissues and Cancer Detection with a Novel Fluorescent Sialidase Substrate
    2014
    Co-Authors: Akira Minami, Tadamune Otsubo, Daisuke Ieno, Kiyoshi Ikeda, Hiroaki Kanazawa, Kosuke Shimizu, Ko Ohata, Tsunehiro Yokochi, Yuuki Horii, Hokuto Fukumoto
    Abstract:

    Sialidase removes Sialic Acid from sialoglycoconjugates and plays crucial roles in many physiological and pathological processes. Various human cancers express an abnormally high level of the plasma membrane-associated sialidase isoform.Visualization of sialidase activity in living mammalian tissues would be useful not only for understanding sialidase functions but also for cancer diagnosis. However, since enzyme activity of mammalian sialidase is remarkably weak compared with that of bacterial and viral sialidases, it has been difficult to detect sialidase activity in mammalian tissues. We synthesized a novel benzothiazolylphenol-based Sialic Acid Derivative (BTP-Neu5Ac) as a fluorescent sialidase substrate. BTP-Neu5Ac can visualize sialidase activities sensitively and selectively in acute rat brain slices. Cancer cells implanted orthotopically in mouse colons and human colon cancers (stages T3-T4) were also clearly detected with BTP-Neu5Ac. Th

Akira Minami - One of the best experts on this subject based on the ideXlab platform.

  • rapid regulation of sialidase activity in response to neural activity and Sialic Acid removal during memory processing in rat hippocampus
    Journal of Biological Chemistry, 2017
    Co-Authors: Akira Minami, Yuuki Horii, Hokuto Fukumoto, Yuko Meguro, Sayaka Ishibashi, Ami Ishii, Mako Shiratori, Saki Sai, Hirotaka Shimizu, Sumika Shimba
    Abstract:

    Sialidase cleaves Sialic Acids on the extracellular cell surface as well as inside the cell and is necessary for normal long-term potentiation (LTP) at mossy fiber-CA3 pyramidal cell synapses and for hippocampus-dependent spatial memory. Here, we investigated in detail the role of sialidase in memory processing. Sialidase activity measured with 4-methylumbelliferyl-α-d-N-acetylneuraminic Acid (4MU-Neu5Ac) or 5-bromo-4-chloroindol-3-yl-α-d-N-acetylneuraminic Acid (X-Neu5Ac) and Fast Red Violet LB was increased by high-K+-induced membrane depolarization. Sialidase activity was also increased by chemical LTP induction with forskolin and activation of BDNF signaling, non-NMDA receptors, or NMDA receptors. The increase in sialidase activity with neural excitation appears to be caused not by secreted sialidase or by an increase in sialidase expression but by a change in the subcellular localization of sialidase. Astrocytes as well as neurons are also involved in the neural activity-dependent increase in sialidase activity. Sialidase activity visualized with a benzothiazolylphenol-based Sialic Acid Derivative (BTP3-Neu5Ac), a highly sensitive histochemical imaging probe for sialidase activity, at the CA3 stratum lucidum of rat acute hippocampal slices was immediately increased in response to LTP-inducible high-frequency stimulation on a time scale of seconds. To obtain direct evidence for Sialic Acid removal on the extracellular cell surface during neural excitation, the extracellular free Sialic Acid level in the hippocampus was monitored using in vivo microdialysis. The free Sialic Acid level was increased by high-K+-induced membrane depolarization. Desialylation also occurred during hippocampus-dependent memory formation in a contextual fear-conditioning paradigm. Our results show that neural activity-dependent desialylation by sialidase may be involved in hippocampal memory processing.

  • Visualization of Sialidase Activity in Mammalian Tissues and Cancer Detection with a Novel Fluorescent Sialidase Substrate
    PLoS ONE, 2014
    Co-Authors: Akira Minami, Tadamune Otsubo, Daisuke Ieno, Kiyoshi Ikeda, Hiroaki Kanazawa, Kosuke Shimizu, Ko Ohata, Tsunehiro Yokochi, Yuuki Horii, Hokuto Fukumoto
    Abstract:

    Sialidase removes Sialic Acid from sialoglycoconjugates and plays crucial roles in many physiological and pathological processes. Various human cancers express an abnormally high level of the plasma membrane-associated sialidase isoform.Visualization of sialidase activity in living mammalian tissues would be useful not only for understanding sialidase functions but also for cancer diagnosis. However, since enzyme activity of mammalian sialidase is remarkably weak compared with that of bacterial and viral sialidases, it has been difficult to detect sialidase activity in mammalian tissues. We synthesized a novel benzothiazolylphenol-based Sialic Acid Derivative (BTP-Neu5Ac) as a fluorescent sialidase substrate. BTP-Neu5Ac can visualize sialidase activities sensitively and selectively in acute rat brain slices. Cancer cells implanted orthotopically in mouse colons and human colon cancers (stages T3-T4) were also clearly detected with BTP-Neu5Ac. The results suggest that BTP-Neu5Ac is useful for histochemical imaging of sialidase activities.

  • Visualization of Sialidase Activity in Mammalian Tissues and Cancer Detection with a Novel Fluorescent Sialidase Substrate
    2014
    Co-Authors: Akira Minami, Tadamune Otsubo, Daisuke Ieno, Kiyoshi Ikeda, Hiroaki Kanazawa, Kosuke Shimizu, Ko Ohata, Tsunehiro Yokochi, Yuuki Horii, Hokuto Fukumoto
    Abstract:

    Sialidase removes Sialic Acid from sialoglycoconjugates and plays crucial roles in many physiological and pathological processes. Various human cancers express an abnormally high level of the plasma membrane-associated sialidase isoform.Visualization of sialidase activity in living mammalian tissues would be useful not only for understanding sialidase functions but also for cancer diagnosis. However, since enzyme activity of mammalian sialidase is remarkably weak compared with that of bacterial and viral sialidases, it has been difficult to detect sialidase activity in mammalian tissues. We synthesized a novel benzothiazolylphenol-based Sialic Acid Derivative (BTP-Neu5Ac) as a fluorescent sialidase substrate. BTP-Neu5Ac can visualize sialidase activities sensitively and selectively in acute rat brain slices. Cancer cells implanted orthotopically in mouse colons and human colon cancers (stages T3-T4) were also clearly detected with BTP-Neu5Ac. Th

Elizabeth Oday - One of the best experts on this subject based on the ideXlab platform.

  • cytidine monophosphate n acetylneuraminic Acid synthetase enhances invasion of human triple negative breast cancer cells
    OncoTargets and Therapy, 2018
    Co-Authors: Elizabeth Oday, Greg E Idos, Collin Hill, Joan W Chen, Gerhard Wagner
    Abstract:

    Background: Cancer cells have altered bioenergetics, which contributes to their ability to proliferate, survive in unusual microenvironments, and invade other tissues. Changes in glucose metabolism can have pleomorphic effects on tumor cells. Methods: To investigate potential mechanisms responsible for the increased malignancy associated with altered glucose metabolism, we used an unbiased nuclear magnetic resonance spectroscopy screening method to identify glucose metabolites differentially produced in a highly malignant human triple-negative breast cancer (TNBC) cell line (BPLER) and a less malignant isogenic TNBC cell line (HMLER). Results: N-acetylneuraminic Acid (Neu5Ac), the predominant Sialic Acid Derivative in mammalian cells, which forms the terminal sugar on mucinous cell surface glycoproteins, was the major glucose metabolite that differed. Neu5Ac was ~7-fold more abundant in BPLER than HMLER. Loss of Neu5Ac by enzymatic removal or siRNA knockdown of cytidine monophosphate N-acetylneuraminic Acid synthetase (CMAS), which activates cellular Sialic Acids for glycoprotein conjugation, had no significant effect on cell proliferation, but decreased the ability of BPLER to invade through a basement membrane. Conversely, overexpressing CMAS in HMLER increased invasivity. TNBCs in The Cancer Genome Atlas also had significantly more CMAS copy number variations and higher mRNA expression than non-TNBC, which have a better prognosis. CMAS knockdown in BPLER ex vivo blocked xenograft formation in mice. Conclusion: Neu5Ac is selectively highly enriched in aggressive TNBC, and CMAS, the enzyme required for sialylation, may play an important role in TNBC tumor formation and invasivity.

Yuuki Horii - One of the best experts on this subject based on the ideXlab platform.

  • rapid regulation of sialidase activity in response to neural activity and Sialic Acid removal during memory processing in rat hippocampus
    Journal of Biological Chemistry, 2017
    Co-Authors: Akira Minami, Yuuki Horii, Hokuto Fukumoto, Yuko Meguro, Sayaka Ishibashi, Ami Ishii, Mako Shiratori, Saki Sai, Hirotaka Shimizu, Sumika Shimba
    Abstract:

    Sialidase cleaves Sialic Acids on the extracellular cell surface as well as inside the cell and is necessary for normal long-term potentiation (LTP) at mossy fiber-CA3 pyramidal cell synapses and for hippocampus-dependent spatial memory. Here, we investigated in detail the role of sialidase in memory processing. Sialidase activity measured with 4-methylumbelliferyl-α-d-N-acetylneuraminic Acid (4MU-Neu5Ac) or 5-bromo-4-chloroindol-3-yl-α-d-N-acetylneuraminic Acid (X-Neu5Ac) and Fast Red Violet LB was increased by high-K+-induced membrane depolarization. Sialidase activity was also increased by chemical LTP induction with forskolin and activation of BDNF signaling, non-NMDA receptors, or NMDA receptors. The increase in sialidase activity with neural excitation appears to be caused not by secreted sialidase or by an increase in sialidase expression but by a change in the subcellular localization of sialidase. Astrocytes as well as neurons are also involved in the neural activity-dependent increase in sialidase activity. Sialidase activity visualized with a benzothiazolylphenol-based Sialic Acid Derivative (BTP3-Neu5Ac), a highly sensitive histochemical imaging probe for sialidase activity, at the CA3 stratum lucidum of rat acute hippocampal slices was immediately increased in response to LTP-inducible high-frequency stimulation on a time scale of seconds. To obtain direct evidence for Sialic Acid removal on the extracellular cell surface during neural excitation, the extracellular free Sialic Acid level in the hippocampus was monitored using in vivo microdialysis. The free Sialic Acid level was increased by high-K+-induced membrane depolarization. Desialylation also occurred during hippocampus-dependent memory formation in a contextual fear-conditioning paradigm. Our results show that neural activity-dependent desialylation by sialidase may be involved in hippocampal memory processing.

  • Visualization of Sialidase Activity in Mammalian Tissues and Cancer Detection with a Novel Fluorescent Sialidase Substrate
    PLoS ONE, 2014
    Co-Authors: Akira Minami, Tadamune Otsubo, Daisuke Ieno, Kiyoshi Ikeda, Hiroaki Kanazawa, Kosuke Shimizu, Ko Ohata, Tsunehiro Yokochi, Yuuki Horii, Hokuto Fukumoto
    Abstract:

    Sialidase removes Sialic Acid from sialoglycoconjugates and plays crucial roles in many physiological and pathological processes. Various human cancers express an abnormally high level of the plasma membrane-associated sialidase isoform.Visualization of sialidase activity in living mammalian tissues would be useful not only for understanding sialidase functions but also for cancer diagnosis. However, since enzyme activity of mammalian sialidase is remarkably weak compared with that of bacterial and viral sialidases, it has been difficult to detect sialidase activity in mammalian tissues. We synthesized a novel benzothiazolylphenol-based Sialic Acid Derivative (BTP-Neu5Ac) as a fluorescent sialidase substrate. BTP-Neu5Ac can visualize sialidase activities sensitively and selectively in acute rat brain slices. Cancer cells implanted orthotopically in mouse colons and human colon cancers (stages T3-T4) were also clearly detected with BTP-Neu5Ac. The results suggest that BTP-Neu5Ac is useful for histochemical imaging of sialidase activities.

  • Visualization of Sialidase Activity in Mammalian Tissues and Cancer Detection with a Novel Fluorescent Sialidase Substrate
    2014
    Co-Authors: Akira Minami, Tadamune Otsubo, Daisuke Ieno, Kiyoshi Ikeda, Hiroaki Kanazawa, Kosuke Shimizu, Ko Ohata, Tsunehiro Yokochi, Yuuki Horii, Hokuto Fukumoto
    Abstract:

    Sialidase removes Sialic Acid from sialoglycoconjugates and plays crucial roles in many physiological and pathological processes. Various human cancers express an abnormally high level of the plasma membrane-associated sialidase isoform.Visualization of sialidase activity in living mammalian tissues would be useful not only for understanding sialidase functions but also for cancer diagnosis. However, since enzyme activity of mammalian sialidase is remarkably weak compared with that of bacterial and viral sialidases, it has been difficult to detect sialidase activity in mammalian tissues. We synthesized a novel benzothiazolylphenol-based Sialic Acid Derivative (BTP-Neu5Ac) as a fluorescent sialidase substrate. BTP-Neu5Ac can visualize sialidase activities sensitively and selectively in acute rat brain slices. Cancer cells implanted orthotopically in mouse colons and human colon cancers (stages T3-T4) were also clearly detected with BTP-Neu5Ac. Th