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alicyclic hydrocarbon resin metablen tp003  (Mitsubishi Rayon CO)

 
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    Mitsubishi Rayon CO alicyclic hydrocarbon resin metablen tp003
    Alicyclic Hydrocarbon Resin Metablen Tp003, supplied by Mitsubishi Rayon CO, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/product/tp003/metablen+tp+001/us10875998-133-4-14
    Average 90 stars, based on 1 article reviews
    alicyclic hydrocarbon resin metablen tp003 - by Bioz Stars, 2026-10
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    other:

    Article Title: Method for integrally molding metal and resin and metal-resin composite structure obtainable by the same
    Article Snippet: In step (4), 97 weight parts of a straight chain polycarbonate PC (IR2200 available from Idemitsu Kosan Co., Ltd.) and 3 weight parts of a flow improver (TP003 available from Mitsubishi Rayon Co., Ltd.) were weighed, and mixed uniformly to obtain a resin mixture.

    Article Title: Polycarbonate compositions and articles comprising the same
    Article Snippet: Flow Promoter, but No alicyclic Hydrocarbon Resin Metablen TP003, a phenylmethacrylate-styrene-acrylonitrile copolymer manufactured by Mitsubishi Rayon Co. Ltd. C. Impact Modifiers Kane Ace M732 (Kaneka Japan), with a styrene-butadiene rubber as the rubber core, a rubber amount of around 70%, a methyl methacrylate-styrene copolymer being the grafting phase, and a particle size ranging between 150 nm and 200 nm.

    Article Title: Thermoplastic resin, molded object, and monomer for thermoplastic resin
    Article Snippet: Examples of the fluidity modifier used in one aspect of the present invention may include “METABLEN TP-001” and “METABLEN TP-003” (product names; manufactured by MITSUBISHI RAYON CO., LTD.).

    Article Title: Polyester carbonate resin, and molded body which is obtained by molding resin composition containing resin
    Article Snippet: Examples of the fluidity modifier used in one aspect of the present invention may include “METABLEN TP-001” and “METABLEN TP-003” (product names; manufactured by MITSUBISHI RAYON CO., LTD.).

    Diffusion-based Assay:

    Article Title: Light diffusing resin composition and light diffusing plate using the same
    Article Snippet: .. Note that, in Table 1, respective polycarbonate resins are as follows: (1) FN1500: aromatic polycarbonate resin (TAFLON FN1500, manufactured by Idemitsu Petrochemical Co., Ltd.); (2) PEP36: phosphorous stabilizer (ADEKASTAB PEP36, manufactured by ASAHI DENKA Co. Ltd.); (3) KMP590: silicone resin particle (manufactured by Shin-Etsu Chemical Co., Ltd.); (4) X-52-1621: silicone diffusion particulate (manufactured by Shin-Etsu Chemical Co., Ltd.); (5) EXL-5136: methacrylate resin (manufactured by Rohm and Haas Company); (6) MBX-20 (manufactured by Sekisui Plastics Co., Ltd.); (7) Tospearl 120:crosslinked silicone resin (manufactured by TOSHBA CORPORATION); (8) BR83: acrylic resin (DIANALBR83, manufactured by Mitsubishi Rayon Co., Ltd.); (9) KR511: organopolysiloxane (manufactured by Shin-Etsu Chemical Co., Ltd.); (10) SH556 (manufactured by Dow Corning Toray Co., Ltd.,; (11) KF56 (manufactured by Shin-Etsu Chemical Co., Ltd.); (12) SH710 (manufactured by Dow Corning Toray Co., Ltd.,; (13) DC3037 (manufactured by Dow Corning Toray Co., Ltd.,; (14) 2021P:alicyclic epoxy compound (CELLOXIDE 2021P, manufactured by Daicel Chemical Industries Ltd.); (15) Chemisoap 79: light-resisting agent (Trade Mark, manufactured by Chemipro Kasei Kaisha, Ltd.); (16) HOSTAVIN B-CAP: light-resisting agent (Trade Name, manufactured by Clariant Japan K.K.); (17) HOSTAVIN VSU: light-resisting agent (Trade Name, manufactured by Clariant Japan K.K.); (18) PR25: light-resisting agent (Trade Name, manufactured by Clariant Japan K.K.); (19) TP003: styrene/phenylmethacrylate copolymer (manufactured by Mitsubishi Rayon Co., Ltd.). ..



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    Fig. 4. Hispidulin and <t>TP003</t> promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.
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    alicyclic hydrocarbon resin metablen tp003  (Mitsubishi Rayon CO)
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    Fig. 4. Hispidulin and <t>TP003</t> promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.
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    metablen tp003  (Mitsubishi Rayon CO)
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    Fig. 4. Hispidulin and <t>TP003</t> promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.
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    Fig. 4. Hispidulin and <t>TP003</t> promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.
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    tp003 2 4 difluoro 5 8 fluoro 7 1 hydroxy 1 methylethyl imidazo 1 2 a pyridin 3 yl  (Tocris)
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    Fig. 4. Hispidulin and <t>TP003</t> promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.
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    flow improver tp003  (Mitsubishi Rayon CO)
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    Fig. 4. Hispidulin and <t>TP003</t> promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.
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    2',4-difluoro-5'-[8-fluoro-7-(1-hydroxy-1-methylethyl)imidazo[1,2- a ]-pyridin-3-yl]-[1,1'-biphenyl]-2-carbonitrile tp003  (Tocris)
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    Fig. 4. Hispidulin and <t>TP003</t> promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.
    2',4 Difluoro 5' [8 Fluoro 7 (1 Hydroxy 1 Methylethyl)imidazo[1,2 A ] Pyridin 3 Yl] [1,1' Biphenyl] 2 Carbonitrile Tp003, supplied by Tocris, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Fig. 4. Hispidulin and TP003 promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.

    Journal: Pharmacological research

    Article Title: Pharmacological chaperones restore proteostasis of epilepsy-associated GABA A receptor variants.

    doi: 10.1016/j.phrs.2024.107356

    Figure Lengend Snippet: Fig. 4. Hispidulin and TP003 promote the functional surface expression of α1 DAVs. a Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on the surface protein expression of the α1 variants in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1 (M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors according to surface biotinylation analysis. Na+/K+ ATPase serves as a plasma membrane protein loading control. Quantification of the surface α1 band intensities was shown on the bottom panels (n = 3). b Effect of Hispidulin (10 µM, 24 h) or TP003 (5 µM, 24 h) on GABA- induced peak current amplitudes in HEK293T cells expressing α1(A322D)β2γ2, α1(D219N)β2γ2, α1(P260L)β2γ2, α1(R214C)β2γ2, α1(S76R)β2γ2, α1(G251D)β2γ2, α1(M263T)β2γ2, or α1(T289P)β2γ2 GABAA receptors. Representative whole-cell voltage-clamp recording traces are shown. The holding voltage was set at −60 mV. Application of GABA (100 μM, 3 s) is indicated by the horizontal bar above the current traces. Quantification of the peak currents (Imax) are shown on the bottom panels (n = 4–11). pA: pico Ampere. c Comparison of the peak current amplitudes of compound (DMSO, Hispidulin, or TP003)-treated α1 variants with those in wild type (WT) receptors. Data was taken from Fig. 2a and Fig. 4b. Each data point is reported as mean ± SEM. One-way ANOVA followed by post-hoc Tukey test was used for statistical analysis. Statistical significance was labelled for the comparison to the DMSO group ((a, b) or WT group (a, b) or WT group (c). NS, not significant; * p < 0.05; ** p < 0.01; *** p < 0.001. Also see Supplementary Fig. S5.

    Article Snippet: Hispidulin (catalog#: 2174), CL218872 (catalog#: 1709), ZK93423 (catalog#: 1994), Bretazenil (catalog#: 3568), CGS20625 (catalog#: 2467), and TP003 (catalog#: 4414) were purchased from Tocris Bioscience.

    Techniques: Functional Assay, Expressing, Clinical Proteomics, Membrane, Control, Comparison

    Fig. 6. Hispidulin and TP003 inhibit the ERAD of the misfolding-prone α1(G251D) variant. a HEK293T cells stably expressing α1(G251D)β2γ2 receptors were treated with DMSO, Hispidulin (10 µM), and TP003 (5 µM) for 24 h. Then cycloheximide (100 μg / mL) (CHX), a potent protein synthesis inhibitor, was added to the cell culture media for the indicated time before cell lysis and Western blot analysis. Quantification of the normalized remaining α1 protein band intensity was shown on the right (n = 3). b Effect of Hispidulin (10 µM, 24 h) and TP003 (5 µM, 24 h) on the protein levels of selected ERAD factors in HEK293T cells stably expressing α1 (G251D)β2γ2 receptors (n = 3). c Effect of Hispidulin (10 µM, 24 h) and TP003 (5 µM, 24 h) on the interactions between α1(G251D) and selected ERAD factors in HEK293T cells stably expressing α1(G251D)β2γ2 receptors. Quantification of the ratio of proteins of interest / α1(G251D) post immunoprecipitation is shown in the right panels (n = 3). IP: immunoprecipitation. Each data point is reported as mean ± SEM. ANOVA followed by post-hoc Tukey test was used to evaluate the statistical significance. Statistical significance was labelled for the comparison to the DMSO treatment group. NS, not significant; *, p < 0.05; **, p < 0.01; ***, p < 0.001.

    Journal: Pharmacological research

    Article Title: Pharmacological chaperones restore proteostasis of epilepsy-associated GABA A receptor variants.

    doi: 10.1016/j.phrs.2024.107356

    Figure Lengend Snippet: Fig. 6. Hispidulin and TP003 inhibit the ERAD of the misfolding-prone α1(G251D) variant. a HEK293T cells stably expressing α1(G251D)β2γ2 receptors were treated with DMSO, Hispidulin (10 µM), and TP003 (5 µM) for 24 h. Then cycloheximide (100 μg / mL) (CHX), a potent protein synthesis inhibitor, was added to the cell culture media for the indicated time before cell lysis and Western blot analysis. Quantification of the normalized remaining α1 protein band intensity was shown on the right (n = 3). b Effect of Hispidulin (10 µM, 24 h) and TP003 (5 µM, 24 h) on the protein levels of selected ERAD factors in HEK293T cells stably expressing α1 (G251D)β2γ2 receptors (n = 3). c Effect of Hispidulin (10 µM, 24 h) and TP003 (5 µM, 24 h) on the interactions between α1(G251D) and selected ERAD factors in HEK293T cells stably expressing α1(G251D)β2γ2 receptors. Quantification of the ratio of proteins of interest / α1(G251D) post immunoprecipitation is shown in the right panels (n = 3). IP: immunoprecipitation. Each data point is reported as mean ± SEM. ANOVA followed by post-hoc Tukey test was used to evaluate the statistical significance. Statistical significance was labelled for the comparison to the DMSO treatment group. NS, not significant; *, p < 0.05; **, p < 0.01; ***, p < 0.001.

    Article Snippet: Hispidulin (catalog#: 2174), CL218872 (catalog#: 1709), ZK93423 (catalog#: 1994), Bretazenil (catalog#: 3568), CGS20625 (catalog#: 2467), and TP003 (catalog#: 4414) were purchased from Tocris Bioscience.

    Techniques: Variant Assay, Stable Transfection, Expressing, Cell Culture, Lysis, Western Blot, Immunoprecipitation, Comparison

    Fig. 8. Proposed mechanism of action of Hispidulin and TP003 on rescuing α1 DAV trafficking. Hispidulin and TP003 act as pharmacological chaperones to bind GABAA receptor variants to stabilize them in the ER. Pharmacological chaperone treatment enhances the assembly of the variants and their forward trafficking to the Golgi and plasma membrane. The effect of Hispidulin and TP003 is also reflected from the enhanced folding and reduced degradation of the variants. Consistently, the interactions between the variants and pro-folding chaperones (BiP and calnexin) and a trafficking factor (LMAN1) are enhanced, whereas the interactions be tween the variants and ERAD factors (Grp94 and VCP) are reduced by pharmacological chaperone treatment.

    Journal: Pharmacological research

    Article Title: Pharmacological chaperones restore proteostasis of epilepsy-associated GABA A receptor variants.

    doi: 10.1016/j.phrs.2024.107356

    Figure Lengend Snippet: Fig. 8. Proposed mechanism of action of Hispidulin and TP003 on rescuing α1 DAV trafficking. Hispidulin and TP003 act as pharmacological chaperones to bind GABAA receptor variants to stabilize them in the ER. Pharmacological chaperone treatment enhances the assembly of the variants and their forward trafficking to the Golgi and plasma membrane. The effect of Hispidulin and TP003 is also reflected from the enhanced folding and reduced degradation of the variants. Consistently, the interactions between the variants and pro-folding chaperones (BiP and calnexin) and a trafficking factor (LMAN1) are enhanced, whereas the interactions be tween the variants and ERAD factors (Grp94 and VCP) are reduced by pharmacological chaperone treatment.

    Article Snippet: Hispidulin (catalog#: 2174), CL218872 (catalog#: 1709), ZK93423 (catalog#: 1994), Bretazenil (catalog#: 3568), CGS20625 (catalog#: 2467), and TP003 (catalog#: 4414) were purchased from Tocris Bioscience.

    Techniques: Clinical Proteomics, Membrane