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  1. Article ; Online: Mouse Specific Cleavage-Resistant RAGE Splice Variant.

    Fukai, Tohru

    PloS one

    2016  Volume 11, Issue 9, Page(s) e0162120

    Language English
    Publishing date 2016-09-21
    Publishing country United States
    Document type Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0162120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Cross-Talk between NADPH Oxidase and Mitochondria: Role in ROS Signaling and Angiogenesis.

    Fukai, Tohru / Ushio-Fukai, Masuko

    Cells

    2020  Volume 9, Issue 8

    Abstract: Angiogenesis, a new vessel formation from the pre-existing ones, is essential for embryonic development, wound repair and treatment of ischemic heart and limb diseases. However, dysregulated angiogenesis contributes to various pathologies such as ... ...

    Abstract Angiogenesis, a new vessel formation from the pre-existing ones, is essential for embryonic development, wound repair and treatment of ischemic heart and limb diseases. However, dysregulated angiogenesis contributes to various pathologies such as diabetic retinopathy, atherosclerosis and cancer. Reactive oxygen species (ROS) derived from NADPH oxidase (NOX) as well as mitochondria play an important role in promoting the angiogenic switch from quiescent endothelial cells (ECs). However, how highly diffusible ROS produced from different sources and location can communicate with each other to regulate angiogenesis remains unclear. To detect a localized ROS signal in distinct subcellular compartments in real time in situ, compartment-specific genetically encoded redox-sensitive fluorescence biosensors have been developed. Recently, the intercellular communication, "cross-talk", between ROS derived from NOX and mitochondria, termed "ROS-induced ROS release", has been proposed as a mechanism for ROS amplification at distinct subcellular compartments, which are essential for activation of redox signaling. This "ROS-induced ROS release" may represent a feed-forward mechanism of localized ROS production to maintain sustained signaling, which can be targeted under pathological conditions with oxidative stress or enhanced to promote therapeutic angiogenesis. In this review, we summarize the recent knowledge regarding the role of the cross-talk between NOX and mitochondria organizing the sustained ROS signaling involved in VEGF signaling, neovascularization and tissue repair.
    MeSH term(s) Animals ; Endothelial Cells/cytology ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Endothelium, Vascular/cytology ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/pathology ; Humans ; Mitochondria/metabolism ; NADPH Oxidases/metabolism ; Neovascularization, Pathologic ; Neovascularization, Physiologic ; Oxidation-Reduction ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Vascular Endothelial Growth Factor A/metabolism
    Chemical Substances Reactive Oxygen Species ; VEGFA protein, human ; Vascular Endothelial Growth Factor A ; NADPH Oxidases (EC 1.6.3.-)
    Language English
    Publishing date 2020-08-06
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells9081849
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  3. Article ; Online: Mouse Specific Cleavage-Resistant RAGE Splice Variant.

    Tohru Fukai

    PLoS ONE, Vol 11, Iss 9, p e

    2016  Volume 0162120

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
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  4. Article ; Online: Cross-Talk between NADPH Oxidase and Mitochondria

    Tohru Fukai / Masuko Ushio-Fukai

    Cells, Vol 9, Iss 1849, p

    Role in ROS Signaling and Angiogenesis

    2020  Volume 1849

    Abstract: Angiogenesis, a new vessel formation from the pre-existing ones, is essential for embryonic development, wound repair and treatment of ischemic heart and limb diseases. However, dysregulated angiogenesis contributes to various pathologies such as ... ...

    Abstract Angiogenesis, a new vessel formation from the pre-existing ones, is essential for embryonic development, wound repair and treatment of ischemic heart and limb diseases. However, dysregulated angiogenesis contributes to various pathologies such as diabetic retinopathy, atherosclerosis and cancer. Reactive oxygen species (ROS) derived from NADPH oxidase (NOX) as well as mitochondria play an important role in promoting the angiogenic switch from quiescent endothelial cells (ECs). However, how highly diffusible ROS produced from different sources and location can communicate with each other to regulate angiogenesis remains unclear. To detect a localized ROS signal in distinct subcellular compartments in real time in situ, compartment-specific genetically encoded redox-sensitive fluorescence biosensors have been developed. Recently, the intercellular communication, “cross-talk”, between ROS derived from NOX and mitochondria, termed “ROS-induced ROS release”, has been proposed as a mechanism for ROS amplification at distinct subcellular compartments, which are essential for activation of redox signaling. This “ROS-induced ROS release” may represent a feed-forward mechanism of localized ROS production to maintain sustained signaling, which can be targeted under pathological conditions with oxidative stress or enhanced to promote therapeutic angiogenesis. In this review, we summarize the recent knowledge regarding the role of the cross-talk between NOX and mitochondria organizing the sustained ROS signaling involved in VEGF signaling, neovascularization and tissue repair.
    Keywords NADPH oxidase ; mitochondria ; reactive oxygen species ; angiogenesis ; redox signaling ; endothelial cell ; Biology (General) ; QH301-705.5
    Subject code 630
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Pentose Pathway Activation Is Superior to Increased Glycolysis for Therapeutic Angiogenesis in Peripheral Arterial Disease.

    Zaied, Abdelrahman A / Ushio-Fukai, Masuko / Fukai, Tohru / Kovacs-Kasa, Anita / Alhusban, Suhib / Sudhahar, Varadarajan / Ganta, Vijay C / Annex, Brian H

    Journal of the American Heart Association

    2023  Volume 12, Issue 7, Page(s) e027986

    Abstract: Background In endothelial cells (ECs), glycolysis, regulated by PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase, isoform-3), is the major metabolic pathway for ATP generation. In preclinical peripheral artery disease models, ... ...

    Abstract Background In endothelial cells (ECs), glycolysis, regulated by PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase, isoform-3), is the major metabolic pathway for ATP generation. In preclinical peripheral artery disease models, VEGF
    MeSH term(s) Mice ; Animals ; Endothelial Cells/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Reactive Oxygen Species/metabolism ; Peripheral Arterial Disease/metabolism ; Hypoxia/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Glycolysis/physiology ; Ischemia/genetics
    Chemical Substances Vascular Endothelial Growth Factor A ; Reactive Oxygen Species ; MicroRNAs
    Language English
    Publishing date 2023-03-28
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2653953-6
    ISSN 2047-9980 ; 2047-9980
    ISSN (online) 2047-9980
    ISSN 2047-9980
    DOI 10.1161/JAHA.122.027986
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Whole-Transcriptome Sequencing Analyses of Nuclear Antixoxidant-1 in Endothelial Cells: Role in Inflammation and Atherosclerosis.

    Sudhahar, Varadarajan / Shi, Yang / Kaplan, Jack H / Ushio-Fukai, Masuko / Fukai, Tohru

    Cells

    2022  Volume 11, Issue 18

    Abstract: Inflammation, oxidative stress, and copper (Cu) play an important role in cardiovascular disease, including atherosclerosis. We previously reported that cytosolic Cu chaperone antioxidant-1 (Atox1) translocates to the nucleus in response to inflammatory ... ...

    Abstract Inflammation, oxidative stress, and copper (Cu) play an important role in cardiovascular disease, including atherosclerosis. We previously reported that cytosolic Cu chaperone antioxidant-1 (Atox1) translocates to the nucleus in response to inflammatory cytokines or exogenous Cu and that Atox1 is localized at the nucleus in the endothelium of inflamed atherosclerotic aorta. However, the roles of nuclear Atox1 and their function are poorly understood. Here we showed that Atox1 deficiency in ApoE
    MeSH term(s) Animals ; Atherosclerosis/genetics ; Copper/metabolism ; Copper Transport Proteins ; Cytokines/metabolism ; Endothelial Cells/metabolism ; Humans ; Inflammation/genetics ; Mice ; Mice, Knockout, ApoE ; Molecular Chaperones/metabolism ; Reactive Oxygen Species/metabolism ; Transcriptome
    Chemical Substances Atox1 protein, mouse ; Copper Transport Proteins ; Cytokines ; Molecular Chaperones ; Reactive Oxygen Species ; Copper (789U1901C5)
    Language English
    Publishing date 2022-09-18
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11182919
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  7. Article ; Online: Uptake mechanism of iron-phytosiderophore from the soil based on the structure of yellow stripe transporter

    Atsushi Yamagata / Yoshiko Murata / Kosuke Namba / Tohru Terada / Shuya Fukai / Mikako Shirouzu

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 12

    Abstract: Iron is an essential mineral in plant physiology. YS1 transporter imports iron–phytosiderophore complex (Fe(III)–DMA) from the soil. Here, the authors describe the cryo-EM structures of barley YS1 in complex with substrate, and a synthetic substrate ... ...

    Abstract Iron is an essential mineral in plant physiology. YS1 transporter imports iron–phytosiderophore complex (Fe(III)–DMA) from the soil. Here, the authors describe the cryo-EM structures of barley YS1 in complex with substrate, and a synthetic substrate analog.
    Keywords Science ; Q
    Language English
    Publishing date 2022-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
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  8. Article ; Online: Uptake mechanism of iron-phytosiderophore from the soil based on the structure of yellow stripe transporter.

    Yamagata, Atsushi / Murata, Yoshiko / Namba, Kosuke / Terada, Tohru / Fukai, Shuya / Shirouzu, Mikako

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 7180

    Abstract: Calcareous soils cover one-third of all land and cause severe growth defects in plants due to the poor water solubility of iron at high pH. Poaceae species use a unique chelation strategy, whereby plants secrete a high-affinity metal chelator, known as ... ...

    Abstract Calcareous soils cover one-third of all land and cause severe growth defects in plants due to the poor water solubility of iron at high pH. Poaceae species use a unique chelation strategy, whereby plants secrete a high-affinity metal chelator, known as phytosiderophores (mugineic acids), and reabsorb the iron-phytosiderophore complex by the yellow stripe 1/yellow stripe 1-like (YS1/YSL) transporter for efficient uptake of iron from the soil. Here, we present three cryo-electron microscopy structures of barley YS1 (HvYS1) in the apo state, in complex with an iron-phytosiderophore complex, Fe(III)-deoxymugineic acid (Fe(III)-DMA), and in complex with the iron-bound synthetic DMA analog (Fe(III)-PDMA). The structures reveal a homodimeric assembly mediated through an anti-parallel β-sheet interaction with cholesterol hemisuccinate. Each protomer adopts an outward open conformation, and Fe(III)-DMA is bound near the extracellular space in the central cavity. Fe(III)-PDMA occupies the same binding site as Fe(III)-DMA, demonstrating that PDMA can function as a potent fertilizer in an essentially identical manner to DMA. Our results provide a structural framework for iron-phytosiderophore recognition and transport by YS1/YSL transporters, which will enable the rational design of new, high-potency fertilizers.
    MeSH term(s) Iron/metabolism ; Soil ; Cryoelectron Microscopy ; Zea mays/metabolism ; Plant Proteins/metabolism ; Membrane Transport Proteins/metabolism ; Plants/metabolism
    Chemical Substances Iron (E1UOL152H7) ; Soil ; Plant Proteins ; Membrane Transport Proteins
    Language English
    Publishing date 2022-11-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-34930-1
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  9. Article: Myeloid Drp1 Deficiency Limits Revascularization in Ischemic Muscles via Inflammatory Macrophage Polarization and Metabolic Reprograming.

    Yadav, Shikha / Ganta, Vijay / Sudhahar, Varadarajan / Ash, Dipankar / Nagarkoti, Sheela / Das, Archita / McMenamin, Margorzata / Kelley, Stephanie / Fukai, Tohru / Ushio-Fukai, Masuko

    bioRxiv : the preprint server for biology

    2023  

    Abstract: In the preclinical model of peripheral arterial disease (PAD), M2-like anti-inflammatory macrophage polarization and angiogenesis are required for revascularization. The regulation of cell metabolism and inflammation in macrophages is tightly linked to ... ...

    Abstract In the preclinical model of peripheral arterial disease (PAD), M2-like anti-inflammatory macrophage polarization and angiogenesis are required for revascularization. The regulation of cell metabolism and inflammation in macrophages is tightly linked to mitochondrial dynamics. Drp1, a mitochondrial fission protein, has shown context-dependent macrophage phenotypes with both pro- and anti-inflammatory characteristics. However, the role of macrophage Drp1 in reparative neovascularization remains unexplored. Here we show that Drp1 expression was significantly increased in F4/80+ macrophages within ischemic muscle at day 3 following hindlimb ischemia (HLI), an animal model of PAD. Myeloid-specific Drp1
    Language English
    Publishing date 2023-11-05
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.11.04.565656
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  10. Article ; Online: Copper transporters and copper chaperones: roles in cardiovascular physiology and disease.

    Fukai, Tohru / Ushio-Fukai, Masuko / Kaplan, Jack H

    American journal of physiology. Cell physiology

    2018  Volume 315, Issue 2, Page(s) C186–C201

    Abstract: Copper (Cu) is an essential micronutrient but excess Cu is potentially toxic. Its important propensity to cycle between two oxidation states accounts for its frequent presence as a cofactor in many physiological processes through Cu-containing enzymes, ... ...

    Abstract Copper (Cu) is an essential micronutrient but excess Cu is potentially toxic. Its important propensity to cycle between two oxidation states accounts for its frequent presence as a cofactor in many physiological processes through Cu-containing enzymes, including mitochondrial energy production (via cytochrome c-oxidase), protection against oxidative stress (via superoxide dismutase), and extracellular matrix stability (via lysyl oxidase). Since free Cu is potentially toxic, the bioavailability of intracellular Cu is tightly controlled by Cu transporters and Cu chaperones. Recent evidence reveals that these Cu transport systems play an essential role in the physiological responses of cardiovascular cells, including cell growth, migration, angiogenesis and wound repair. In response to growth factors, cytokines, and hypoxia, their expression, subcellular localization, and function are tightly regulated. Cu transport systems and their regulators have also been linked to various cardiovascular pathophysiologies such as hypertension, inflammation, atherosclerosis, diabetes, cardiac hypertrophy, and cardiomyopathy. A greater appreciation of the central importance of Cu transporters and Cu chaperones in cell signaling and gene expression in cardiovascular biology offers the possibility of identifying new therapeutic targets for cardiovascular disease.
    MeSH term(s) Animals ; Cardiovascular Diseases/metabolism ; Cardiovascular Diseases/pathology ; Cardiovascular System/metabolism ; Cardiovascular System/physiopathology ; Cation Transport Proteins/metabolism ; Copper/metabolism ; Gene Expression/physiology ; Humans ; Molecular Chaperones/metabolism ; Signal Transduction/physiology
    Chemical Substances Cation Transport Proteins ; Molecular Chaperones ; Copper (789U1901C5)
    Language English
    Publishing date 2018-06-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 392098-7
    ISSN 1522-1563 ; 0363-6143
    ISSN (online) 1522-1563
    ISSN 0363-6143
    DOI 10.1152/ajpcell.00132.2018
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