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  1. Article ; Online: Oxidant-resistant LRRC8A/C anion channels support superoxide production by NADPH oxidase 1.

    Choi, Hyehun / Rohrbough, Jeffrey C / Nguyen, Hong N / Dikalova, Anna / Lamb, Fred S

    The Journal of physiology

    2021  Volume 599, Issue 12, Page(s) 3013–3036

    Abstract: Key points: LRRC8A-containing anion channels associate with NADPH oxidase 1 (Nox1) and regulate superoxide production and tumour necrosis factor-α (TNFα) signalling. Here we show that LRRC8C and 8D also co-immunoprecipitate with Nox1 in vascular smooth ... ...

    Abstract Key points: LRRC8A-containing anion channels associate with NADPH oxidase 1 (Nox1) and regulate superoxide production and tumour necrosis factor-α (TNFα) signalling. Here we show that LRRC8C and 8D also co-immunoprecipitate with Nox1 in vascular smooth muscle cells. LRRC8C knockdown inhibited TNFα-induced O
    Abstract: Tumour necrosis factor-α (TNFα) activates NADPH oxidase 1 (Nox1) in vascular smooth muscle cells (VSMCs), producing superoxide (O
    MeSH term(s) Anions ; HEK293 Cells ; Humans ; Membrane Proteins ; NADPH Oxidase 1 ; Oxidants ; Superoxides
    Chemical Substances Anions ; LRRC8A protein, human ; Membrane Proteins ; Oxidants ; Superoxides (11062-77-4) ; NADPH Oxidase 1 (EC 1.6.3.-)
    Language English
    Publishing date 2021-05-26
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP281577
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.65: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Chloride Channel-3 (ClC-3) Modifies the Trafficking of Leucine-Rich Repeat-Containing 8A (LRRC8A) Anion Channels.

    Stark, Ryan J / Nguyen, Hong N / Bacon, Matthew K / Rohrbough, Jeffrey C / Choi, Hyehun / Lamb, Fred S

    The Journal of membrane biology

    2022  Volume 256, Issue 2, Page(s) 125–135

    Abstract: Chloride channel-3 (ClC-3) ... ...

    Abstract Chloride channel-3 (ClC-3) Cl
    MeSH term(s) Humans ; Membrane Proteins/metabolism ; Leucine ; HEK293 Cells ; Chloride Channels/genetics ; Chloride Channels/metabolism ; Anions/metabolism
    Chemical Substances Membrane Proteins ; Leucine (GMW67QNF9C) ; Chloride Channels ; Anions ; LRRC8A protein, human
    Language English
    Publishing date 2022-11-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3082-x
    ISSN 1432-1424 ; 0022-2631
    ISSN (online) 1432-1424
    ISSN 0022-2631
    DOI 10.1007/s00232-022-00271-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 613: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: LRRC8A anion channels modulate vascular reactivity via association with myosin phosphatase rho interacting protein.

    Choi, Hyehun / Miller, Michael R / Nguyen, Hong-Ngan / Rohrbough, Jeffrey C / Koch, Stephen R / Boatwright, Naoko / Yarboro, Michael T / Sah, Rajan / McDonald, W Hayes / Reese, J Jeffrey / Stark, Ryan J / Lamb, Fred S

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2023  Volume 37, Issue 7, Page(s) e23028

    Abstract: Leucine-rich repeat containing 8A (LRRC8A) volume regulated anion channels (VRACs) are activated by inflammatory and pro-contractile stimuli including tumor necrosis factor alpha (TNFα), angiotensin II and stretch. LRRC8A associates with NADPH oxidase 1 ( ...

    Abstract Leucine-rich repeat containing 8A (LRRC8A) volume regulated anion channels (VRACs) are activated by inflammatory and pro-contractile stimuli including tumor necrosis factor alpha (TNFα), angiotensin II and stretch. LRRC8A associates with NADPH oxidase 1 (Nox1) and supports extracellular superoxide production. We tested the hypothesis that VRACs modulate TNFα signaling and vasomotor function in mice lacking LRRC8A exclusively in vascular smooth muscle cells (VSMCs, Sm22α-Cre, Knockout). Knockout (KO) mesenteric vessels contracted normally but relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) was enhanced compared to wild type (WT). Forty-eight hours of ex vivo exposure to TNFα (10 ng/mL) enhanced contraction to norepinephrine (NE) and markedly impaired dilation to ACh and SNP in WT but not KO vessels. VRAC blockade (carbenoxolone, CBX, 100 μM, 20 min) enhanced dilation of control rings and restored impaired dilation following TNFα exposure. Myogenic tone was absent in KO rings. LRRC8A immunoprecipitation followed by mass spectroscopy identified 33 proteins that interacted with LRRC8A. Among them, the myosin phosphatase rho-interacting protein (MPRIP) links RhoA, MYPT1 and actin. LRRC8A-MPRIP co-localization was confirmed by confocal imaging of tagged proteins, Proximity Ligation Assays, and IP/western blots. siLRRC8A or CBX treatment decreased RhoA activity in VSMCs, and MYPT1 phosphorylation was reduced in KO mesenteries suggesting that reduced ROCK activity contributes to enhanced relaxation. MPRIP was a target of redox modification, becoming oxidized (sulfenylated) after TNFα exposure. Interaction of LRRC8A with MPRIP may allow redox regulation of the cytoskeleton by linking Nox1 activation to impaired vasodilation. This identifies VRACs as potential targets for treatment or prevention of vascular disease.
    MeSH term(s) Animals ; Mice ; Acetylcholine/pharmacology ; Anions ; Membrane Proteins/genetics ; Mice, Knockout ; Myosin-Light-Chain Phosphatase ; Signal Transduction ; Tumor Necrosis Factor-alpha/pharmacology ; Muscle, Smooth, Vascular/cytology ; Muscle, Smooth, Vascular/metabolism ; Muscle, Smooth, Vascular/physiology
    Chemical Substances Acetylcholine (N9YNS0M02X) ; Anions ; LRRC8A protein, mouse ; Membrane Proteins ; Myosin-Light-Chain Phosphatase (EC 3.1.3.53) ; Tumor Necrosis Factor-alpha ; Mprip protein, mouse
    Language English
    Publishing date 2023-06-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.202300561R
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2266: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 296: Show issues

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  4. Article: LRRC8A anion channels modulate vasodilation via association with Myosin Phosphatase Rho Interacting Protein (MPRIP).

    Choi, Hyehun / Miller, Michael R / Nguyen, Hong-Ngan / Rohrbough, Jeffrey C / Koch, Stephen R / Boatwright, Naoko / Yarboro, Michael T / Sah, Rajan / McDonald, W Hayes / Reese, J Jeffrey / Stark, Ryan J / Lamb, Fred S

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Background: In vascular smooth muscle cells (VSMCs), LRRC8A volume regulated anion channels (VRACs) are activated by inflammatory and pro-contractile stimuli including tumor necrosis factor alpha (TNFα), angiotensin II and stretch. LRRC8A physically ... ...

    Abstract Background: In vascular smooth muscle cells (VSMCs), LRRC8A volume regulated anion channels (VRACs) are activated by inflammatory and pro-contractile stimuli including tumor necrosis factor alpha (TNFα), angiotensin II and stretch. LRRC8A physically associates with NADPH oxidase 1 (Nox1) and supports its production of extracellular superoxide (O
    Methods and results: Mice lacking LRRC8A exclusively in VSMCs (Sm22α-Cre, KO) were used to assess the role of VRACs in TNFα signaling and vasomotor function. KO mesenteric vessels contracted normally to KCl and phenylephrine, but relaxation to acetylcholine (ACh) and sodium nitroprusside (SNP) was enhanced compared to wild type (WT). 48 hours of
    Conclusions: Interaction of Nox1/LRRC8A with MPRIP/RhoA/MYPT1/actin may allow redox regulation of the cytoskeleton and link Nox1 activation to both inflammation and vascular contractility.
    Language English
    Publishing date 2023-03-10
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.03.08.531807
    Database MEDical Literature Analysis and Retrieval System OnLINE

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