sb202190  (Cayman Chemical)

 
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    Name:
    SB 202190
    Description:
    SB 202190 is a selective potent cell permeable inhibitor of p38 MAP kinases inhibiting p38α SAPK2A MAPK14 and p38β SAPK2B MAPK11 with IC values of 50 and 100 nM respectively When tested at 10 μM SB 202190 has negligible effects on a range of other kinases including other MAP kinases ERKs JNKs Pyridinyl imidazole inhibitors including this compound directly bind p38 MAP kinases in the ATP binding pocket Recently SB 202190 has been used to elucidate the roles of p38 MAP kinases in inflammatory cytokine expression nicotine induced receptor expression and HIV mediated depressive disorder
    Catalog Number:
    10010399
    Price:
    $29
    Purity:
    ≥98%
    Size:
    10 mg
    Formula:
    A crystalline solid
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    Structured Review

    Cayman Chemical sb202190
    TLR2-MAPK-ERK1/2 signaling cascade is required for the induction of VEGFA and Snail-1 by PCN033 ( A ) Phosphorylation of ERK1/2 along with PCN033 infection. The β-actin was detected as the loading control. ( B ) Densitometrical analysis of the ERK1/2 activation in hBMEC 2 h post-infection, compared with that in uninfected cells. Data are calculated as the ratio of phospho-ERK1/2 to total ERK1/2. ( C ) Effects of the MAPK signaling inhibitors on the PCN033-induced upregulation of VEGFA. U0126 (selective inhibitor of ERK1/2) and <t>SB202190</t> (selective inhibitor of p38) could significantly decrease the PCN033-induced upregulation of VEGFA, while SP600125 (specific inhibitor of JNK) could not. ( D ) Effects of the MAPK signaling inhibitors on the PCN033-induced upregulation of Snail-1. Selective ERK1/2 inhibitor U0126 could completely block the PCN033-induced upregulation of Snail-1. ( E – F ) Snail-1 knocking-down via shRNA in hBMEC did not affect the induction of VEGFA by PCN033, while blocking VEGFA pathway significantly decreased the upregulation of Snail-1. ( G – H ) Effects of the VEGFR inhibitors on PCN033-induced activation of ERK1/2 and the densitometric analysis. ( I – J ) TLR2 agonist Pam3CSK4 induced the activation of ERK1/2 in a dose-dependent manner. ( K – L ) Pam3CSK4 dose-dependently induced the upregulation of Snail-1 and VEGFA in hBMEC. Results are expressed as mean ± SD from three independent assays.
    SB 202190 is a selective potent cell permeable inhibitor of p38 MAP kinases inhibiting p38α SAPK2A MAPK14 and p38β SAPK2B MAPK11 with IC values of 50 and 100 nM respectively When tested at 10 μM SB 202190 has negligible effects on a range of other kinases including other MAP kinases ERKs JNKs Pyridinyl imidazole inhibitors including this compound directly bind p38 MAP kinases in the ATP binding pocket Recently SB 202190 has been used to elucidate the roles of p38 MAP kinases in inflammatory cytokine expression nicotine induced receptor expression and HIV mediated depressive disorder
    https://www.bioz.com/result/sb202190/product/Cayman Chemical
    Average 94 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    sb202190 - by Bioz Stars, 2021-03
    94/100 stars

    Images

    1) Product Images from "Induction of VEGFA and Snail-1 by meningitic Escherichia coli mediates disruption of the blood-brain barrier"

    Article Title: Induction of VEGFA and Snail-1 by meningitic Escherichia coli mediates disruption of the blood-brain barrier

    Journal: Oncotarget

    doi: 10.18632/oncotarget.11696

    TLR2-MAPK-ERK1/2 signaling cascade is required for the induction of VEGFA and Snail-1 by PCN033 ( A ) Phosphorylation of ERK1/2 along with PCN033 infection. The β-actin was detected as the loading control. ( B ) Densitometrical analysis of the ERK1/2 activation in hBMEC 2 h post-infection, compared with that in uninfected cells. Data are calculated as the ratio of phospho-ERK1/2 to total ERK1/2. ( C ) Effects of the MAPK signaling inhibitors on the PCN033-induced upregulation of VEGFA. U0126 (selective inhibitor of ERK1/2) and SB202190 (selective inhibitor of p38) could significantly decrease the PCN033-induced upregulation of VEGFA, while SP600125 (specific inhibitor of JNK) could not. ( D ) Effects of the MAPK signaling inhibitors on the PCN033-induced upregulation of Snail-1. Selective ERK1/2 inhibitor U0126 could completely block the PCN033-induced upregulation of Snail-1. ( E – F ) Snail-1 knocking-down via shRNA in hBMEC did not affect the induction of VEGFA by PCN033, while blocking VEGFA pathway significantly decreased the upregulation of Snail-1. ( G – H ) Effects of the VEGFR inhibitors on PCN033-induced activation of ERK1/2 and the densitometric analysis. ( I – J ) TLR2 agonist Pam3CSK4 induced the activation of ERK1/2 in a dose-dependent manner. ( K – L ) Pam3CSK4 dose-dependently induced the upregulation of Snail-1 and VEGFA in hBMEC. Results are expressed as mean ± SD from three independent assays.
    Figure Legend Snippet: TLR2-MAPK-ERK1/2 signaling cascade is required for the induction of VEGFA and Snail-1 by PCN033 ( A ) Phosphorylation of ERK1/2 along with PCN033 infection. The β-actin was detected as the loading control. ( B ) Densitometrical analysis of the ERK1/2 activation in hBMEC 2 h post-infection, compared with that in uninfected cells. Data are calculated as the ratio of phospho-ERK1/2 to total ERK1/2. ( C ) Effects of the MAPK signaling inhibitors on the PCN033-induced upregulation of VEGFA. U0126 (selective inhibitor of ERK1/2) and SB202190 (selective inhibitor of p38) could significantly decrease the PCN033-induced upregulation of VEGFA, while SP600125 (specific inhibitor of JNK) could not. ( D ) Effects of the MAPK signaling inhibitors on the PCN033-induced upregulation of Snail-1. Selective ERK1/2 inhibitor U0126 could completely block the PCN033-induced upregulation of Snail-1. ( E – F ) Snail-1 knocking-down via shRNA in hBMEC did not affect the induction of VEGFA by PCN033, while blocking VEGFA pathway significantly decreased the upregulation of Snail-1. ( G – H ) Effects of the VEGFR inhibitors on PCN033-induced activation of ERK1/2 and the densitometric analysis. ( I – J ) TLR2 agonist Pam3CSK4 induced the activation of ERK1/2 in a dose-dependent manner. ( K – L ) Pam3CSK4 dose-dependently induced the upregulation of Snail-1 and VEGFA in hBMEC. Results are expressed as mean ± SD from three independent assays.

    Techniques Used: Infection, Activation Assay, Blocking Assay, shRNA

    2) Product Images from "Leptin regulation of the p53-HIF1α/PKM2-aromatase axis in breast adipose stromal cells – a novel mechanism for the obesity-breast cancer link"

    Article Title: Leptin regulation of the p53-HIF1α/PKM2-aromatase axis in breast adipose stromal cells – a novel mechanism for the obesity-breast cancer link

    Journal: International journal of obesity (2005)

    doi: 10.1038/ijo.2017.273

    Leptin induces aromatase gene expression via effects on PKC and ERK1/2 Immortalized ASCs were treated for 24h with 0–100 ng/ml leptin. Following treatment, aromatase (A) activity, (B) mRNA expression and (C) promoter PII activity were examined and found to be increased in a dose-dependent manner. (D) Leptin stimulated the translocation of cytosolic PKC to the membrane. (E) Treatment of cells with PKC inhibitor calphostin (Cal.) led to the dose-dependent inhibition of the leptin-mediated increase in aromatase activity. ASCs were pre-treated with vehicle or the indicated concentrations of calphostin (Cal.) for 2h. Subsequently, cells were treated with leptin or leptin plus calphostin for 24 h. (F; top) Leptin treatment caused a transient increased in ERK1/2 phosphorylation. ASCs were treated with vehicle or 100 ng/ml leptin for the indicated times. Cell lysates were subjected to Western Blotting. (F; bottom) Treatment with MEK1/2 inhibitor PD98059 caused a dose-dependent decrease in the leptin-mediated induction of aromatase activity. ASCs were pretreated with vehicle or the indicated concentrations of PD98059 for 2h. Subsequently, the cells received vehicle, 100ng/ml leptin or leptin + 25–100 uM PD98059 for 24h. (G,H; top) Western blotting demonstrating time-dependent effects of leptin on phosphorylation of JNK (G) and p38 (H). No effect of inhibitors of JNK or p38 MAPK on aromatase activity was observed (G,H; bottom). ASCs were pretreated with indicated concentrations of SP600125 or SB202190, respectively for 2h. Subsequently, cells received vehicle, 100ng/ml leptin or leptin + the indicated concentrations of SP600125 or SB202190 for 24h. Aromatase activity is expressed as femtomoles/μg protein. Data are presented as mean ± SD, n=6. C: control; L: leptin.
    Figure Legend Snippet: Leptin induces aromatase gene expression via effects on PKC and ERK1/2 Immortalized ASCs were treated for 24h with 0–100 ng/ml leptin. Following treatment, aromatase (A) activity, (B) mRNA expression and (C) promoter PII activity were examined and found to be increased in a dose-dependent manner. (D) Leptin stimulated the translocation of cytosolic PKC to the membrane. (E) Treatment of cells with PKC inhibitor calphostin (Cal.) led to the dose-dependent inhibition of the leptin-mediated increase in aromatase activity. ASCs were pre-treated with vehicle or the indicated concentrations of calphostin (Cal.) for 2h. Subsequently, cells were treated with leptin or leptin plus calphostin for 24 h. (F; top) Leptin treatment caused a transient increased in ERK1/2 phosphorylation. ASCs were treated with vehicle or 100 ng/ml leptin for the indicated times. Cell lysates were subjected to Western Blotting. (F; bottom) Treatment with MEK1/2 inhibitor PD98059 caused a dose-dependent decrease in the leptin-mediated induction of aromatase activity. ASCs were pretreated with vehicle or the indicated concentrations of PD98059 for 2h. Subsequently, the cells received vehicle, 100ng/ml leptin or leptin + 25–100 uM PD98059 for 24h. (G,H; top) Western blotting demonstrating time-dependent effects of leptin on phosphorylation of JNK (G) and p38 (H). No effect of inhibitors of JNK or p38 MAPK on aromatase activity was observed (G,H; bottom). ASCs were pretreated with indicated concentrations of SP600125 or SB202190, respectively for 2h. Subsequently, cells received vehicle, 100ng/ml leptin or leptin + the indicated concentrations of SP600125 or SB202190 for 24h. Aromatase activity is expressed as femtomoles/μg protein. Data are presented as mean ± SD, n=6. C: control; L: leptin.

    Techniques Used: Expressing, Activity Assay, Translocation Assay, Inhibition, Western Blot

    3) Product Images from "A MicroRNA Derived from Adenovirus Virus-Associated RNAII Promotes Virus Infection via Posttranscriptional Gene Silencing"

    Article Title: A MicroRNA Derived from Adenovirus Virus-Associated RNAII Promotes Virus Infection via Posttranscriptional Gene Silencing

    Journal: Journal of Virology

    doi: 10.1128/JVI.01265-18

    JNK signaling is involved in mivaRNAII-mediated promotion of Ad infection. (A) HeLa cells were transfected with 3′-mivaRNAII (3′-mivaRNAII-138) mimic or siCUL4A at 50 nM for 48 h, followed by infection with Ad (WT-Ad, Sub720) at 100 VPs/cell. After 24 h of incubation, protein levels of c-Jun and ATF2 were evaluated by Western blotting analysis. (B and C) HeLa cells were treated with JNK inhibitors (10 mM SP600125 or 20 mM CEP1347), followed by infection with WT-Ad at 100 VPs/cell. (B) After 12 h of incubation, mRNA levels of the Ad genes were determined by qRT-PCR analysis. (C) After 24 h of incubation, Ad genome copy numbers were determined and expressed as relative values (dimethyl sulfoxide [DMSO] = 1). (D and E) HeLa cells were treated with 10 mM U0126 (an ERK inhibitor) or 20 mM SB202190 (a p38 inhibitor) and infected with WT-Ad at 100 VPs/cell. (D) After 12 h of incubation, mRNA levels of the Ad genes were determined by qRT-PCR analysis. (E) After 24 h of incubation, Ad genome copy numbers were determined. These data are expressed as means ± SD (B and C, n = 4; D and E, n = 3).
    Figure Legend Snippet: JNK signaling is involved in mivaRNAII-mediated promotion of Ad infection. (A) HeLa cells were transfected with 3′-mivaRNAII (3′-mivaRNAII-138) mimic or siCUL4A at 50 nM for 48 h, followed by infection with Ad (WT-Ad, Sub720) at 100 VPs/cell. After 24 h of incubation, protein levels of c-Jun and ATF2 were evaluated by Western blotting analysis. (B and C) HeLa cells were treated with JNK inhibitors (10 mM SP600125 or 20 mM CEP1347), followed by infection with WT-Ad at 100 VPs/cell. (B) After 12 h of incubation, mRNA levels of the Ad genes were determined by qRT-PCR analysis. (C) After 24 h of incubation, Ad genome copy numbers were determined and expressed as relative values (dimethyl sulfoxide [DMSO] = 1). (D and E) HeLa cells were treated with 10 mM U0126 (an ERK inhibitor) or 20 mM SB202190 (a p38 inhibitor) and infected with WT-Ad at 100 VPs/cell. (D) After 12 h of incubation, mRNA levels of the Ad genes were determined by qRT-PCR analysis. (E) After 24 h of incubation, Ad genome copy numbers were determined. These data are expressed as means ± SD (B and C, n = 4; D and E, n = 3).

    Techniques Used: Infection, Transfection, Incubation, Western Blot, Quantitative RT-PCR

    4) Product Images from "Trained murine mesenchymal stem cells have anti-inflammatory effect on macrophages, but defective regulation on T-cell proliferation"

    Article Title: Trained murine mesenchymal stem cells have anti-inflammatory effect on macrophages, but defective regulation on T-cell proliferation

    Journal: The FASEB Journal

    doi: 10.1096/fj.201801845R

    Involvement of histone methylation and JNK signaling pathway in the induction of iNOS expression in LPS-trained MSCs. A ) Illustration of mechanistic study with epigenetic or signaling pathway inhibitors. I + T, IFN-γ plus TNF-α; qPCR, quantitative PCR; D, day; W/WO, with/without. B ) The expression of iNOS in LPS-trained MSCs with epigenetic inhibitors. AA, anacardic acid; D-α, D-α-hydroxyglutaric acid; L-α, L-α-hydroxyglutaric acid; MTA, 5′-deoxy-5′-methylthioadenosine; Par, pargyline. C ) Downstream signaling pathway of TLR-4 activation. D ) The expression of iNOS in LPS-trained MSCs with pathway inhibitors. Akt I, Akt inhibitor VIII; IKK2I, IKK2 inhibitor VI; MEK I, PD98059, JNK I, SP600125; p38 I, SB202190. * P
    Figure Legend Snippet: Involvement of histone methylation and JNK signaling pathway in the induction of iNOS expression in LPS-trained MSCs. A ) Illustration of mechanistic study with epigenetic or signaling pathway inhibitors. I + T, IFN-γ plus TNF-α; qPCR, quantitative PCR; D, day; W/WO, with/without. B ) The expression of iNOS in LPS-trained MSCs with epigenetic inhibitors. AA, anacardic acid; D-α, D-α-hydroxyglutaric acid; L-α, L-α-hydroxyglutaric acid; MTA, 5′-deoxy-5′-methylthioadenosine; Par, pargyline. C ) Downstream signaling pathway of TLR-4 activation. D ) The expression of iNOS in LPS-trained MSCs with pathway inhibitors. Akt I, Akt inhibitor VIII; IKK2I, IKK2 inhibitor VI; MEK I, PD98059, JNK I, SP600125; p38 I, SB202190. * P

    Techniques Used: Methylation, Expressing, Real-time Polymerase Chain Reaction, Activation Assay

    Related Articles

    other:

    Article Title: A MicroRNA Derived from Adenovirus Virus-Associated RNAII Promotes Virus Infection via Posttranscriptional Gene Silencing
    Article Snippet: SB202190 and U-0126 were purchased from Cayman Chemical (Ann Arbor, MI).

    Article Title: Cellular aging contributes to failure of cold-induced beige adipocyte formation in old mice and humans
    Article Snippet: SB202190 (SB) was purchased from Cayman Chemicals and dissolved in DMSO.

    Cell Culture:

    Article Title: Dose-dependent functions of fibroblast growth factor 9 regulate the fate of murine XY primordial germ cells
    Article Snippet: Isolated PGCs were treated with 0.2–100 ng/ml FGF9 (Sigma-Aldrich, St. Louis, MO). .. In some experiments, PGCs were cultured with p38 inhibitors (BIRB796; Cayman Chemical Company, Ann Arbor, MI, SB202190; Sigma-Aldrich) at 10 μM or MEK inhibitor (U0126; Cayman Chemical Company) at 1 or 10 μM. ..

    Inhibition:

    Article Title: Early spatiotemporal-specific changes in intermediate signals are predictive of cytotoxic sensitivity to TNFα and co-treatments
    Article Snippet: .. To examine the effect of inhibition of intracellular signaling proteins on the TNFα sensitivity of H460 cells, we added 10 μM of BI-D1870 (#15264, Cayman Chemicals), TPCA-1 (#2559, R & D Systems), SP600125 (#10010466, Cayman Chemicals), SB200190 (#10010399, Cayman Chemicals), or DMSO control (0.1%) to the cyclohexamide and BSA/TNFα solutions. ..

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    Cayman Chemical sb202190 sb
    Inhibiting p38/MAPK in SMA cells stimulates cold-induced beiging (A-D) Schema- Six month old TM induced SMA-Cre ERT2 ; R26R RFP male mice were administered vehicle or <t>SB202190</t> (75 μg/mouse/day) for five consecutive days. Mice were randomized to room temperature or cold for seven days (A). (B) H E staining. (C) UCP1 IHC. (D) SMA/RFP fluorescence fate mapping. (E-H) Schema- Six-month-old TM induced SMA-Cre ERT2 and SMA-Cre ERT2 ; PPARγ fl/fl male mice were administered vehicle or SB (75 μg/mouse/day) for five days and subjected to room or cold temperatures for seven days. (G) H E staining. (H) UCP1 IHC. Scale bar = 200 μm.
    Sb202190 Sb, supplied by Cayman Chemical, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/sb202190 sb/product/Cayman Chemical
    Average 93 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    sb202190 sb - by Bioz Stars, 2021-03
    93/100 stars
      Buy from Supplier

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    Inhibiting p38/MAPK in SMA cells stimulates cold-induced beiging (A-D) Schema- Six month old TM induced SMA-Cre ERT2 ; R26R RFP male mice were administered vehicle or SB202190 (75 μg/mouse/day) for five consecutive days. Mice were randomized to room temperature or cold for seven days (A). (B) H E staining. (C) UCP1 IHC. (D) SMA/RFP fluorescence fate mapping. (E-H) Schema- Six-month-old TM induced SMA-Cre ERT2 and SMA-Cre ERT2 ; PPARγ fl/fl male mice were administered vehicle or SB (75 μg/mouse/day) for five days and subjected to room or cold temperatures for seven days. (G) H E staining. (H) UCP1 IHC. Scale bar = 200 μm.

    Journal: Cell metabolism

    Article Title: Cellular aging contributes to failure of cold-induced beige adipocyte formation in old mice and humans

    doi: 10.1016/j.cmet.2016.10.023

    Figure Lengend Snippet: Inhibiting p38/MAPK in SMA cells stimulates cold-induced beiging (A-D) Schema- Six month old TM induced SMA-Cre ERT2 ; R26R RFP male mice were administered vehicle or SB202190 (75 μg/mouse/day) for five consecutive days. Mice were randomized to room temperature or cold for seven days (A). (B) H E staining. (C) UCP1 IHC. (D) SMA/RFP fluorescence fate mapping. (E-H) Schema- Six-month-old TM induced SMA-Cre ERT2 and SMA-Cre ERT2 ; PPARγ fl/fl male mice were administered vehicle or SB (75 μg/mouse/day) for five days and subjected to room or cold temperatures for seven days. (G) H E staining. (H) UCP1 IHC. Scale bar = 200 μm.

    Article Snippet: SB202190 (SB) was purchased from Cayman Chemicals and dissolved in DMSO.

    Techniques: Mouse Assay, Staining, Immunohistochemistry, Fluorescence

    Pharmacologically targeting p38/MAPK in old SMA+ mural cells rejuvenates beige formation (A-C) Total SV cells were isolated from six month old C57/Bl6 male mice (A, B) or SV cells generated from aged human samples. Cells were treated with vehicle or SB202190 (5 μM) for 15 consecutive days. mRNA of senescence markers was examined. *P

    Journal: Cell metabolism

    Article Title: Cellular aging contributes to failure of cold-induced beige adipocyte formation in old mice and humans

    doi: 10.1016/j.cmet.2016.10.023

    Figure Lengend Snippet: Pharmacologically targeting p38/MAPK in old SMA+ mural cells rejuvenates beige formation (A-C) Total SV cells were isolated from six month old C57/Bl6 male mice (A, B) or SV cells generated from aged human samples. Cells were treated with vehicle or SB202190 (5 μM) for 15 consecutive days. mRNA of senescence markers was examined. *P

    Article Snippet: SB202190 (SB) was purchased from Cayman Chemicals and dissolved in DMSO.

    Techniques: Isolation, Mouse Assay, Generated

    TLR2-MAPK-ERK1/2 signaling cascade is required for the induction of VEGFA and Snail-1 by PCN033 ( A ) Phosphorylation of ERK1/2 along with PCN033 infection. The β-actin was detected as the loading control. ( B ) Densitometrical analysis of the ERK1/2 activation in hBMEC 2 h post-infection, compared with that in uninfected cells. Data are calculated as the ratio of phospho-ERK1/2 to total ERK1/2. ( C ) Effects of the MAPK signaling inhibitors on the PCN033-induced upregulation of VEGFA. U0126 (selective inhibitor of ERK1/2) and SB202190 (selective inhibitor of p38) could significantly decrease the PCN033-induced upregulation of VEGFA, while SP600125 (specific inhibitor of JNK) could not. ( D ) Effects of the MAPK signaling inhibitors on the PCN033-induced upregulation of Snail-1. Selective ERK1/2 inhibitor U0126 could completely block the PCN033-induced upregulation of Snail-1. ( E – F ) Snail-1 knocking-down via shRNA in hBMEC did not affect the induction of VEGFA by PCN033, while blocking VEGFA pathway significantly decreased the upregulation of Snail-1. ( G – H ) Effects of the VEGFR inhibitors on PCN033-induced activation of ERK1/2 and the densitometric analysis. ( I – J ) TLR2 agonist Pam3CSK4 induced the activation of ERK1/2 in a dose-dependent manner. ( K – L ) Pam3CSK4 dose-dependently induced the upregulation of Snail-1 and VEGFA in hBMEC. Results are expressed as mean ± SD from three independent assays.

    Journal: Oncotarget

    Article Title: Induction of VEGFA and Snail-1 by meningitic Escherichia coli mediates disruption of the blood-brain barrier

    doi: 10.18632/oncotarget.11696

    Figure Lengend Snippet: TLR2-MAPK-ERK1/2 signaling cascade is required for the induction of VEGFA and Snail-1 by PCN033 ( A ) Phosphorylation of ERK1/2 along with PCN033 infection. The β-actin was detected as the loading control. ( B ) Densitometrical analysis of the ERK1/2 activation in hBMEC 2 h post-infection, compared with that in uninfected cells. Data are calculated as the ratio of phospho-ERK1/2 to total ERK1/2. ( C ) Effects of the MAPK signaling inhibitors on the PCN033-induced upregulation of VEGFA. U0126 (selective inhibitor of ERK1/2) and SB202190 (selective inhibitor of p38) could significantly decrease the PCN033-induced upregulation of VEGFA, while SP600125 (specific inhibitor of JNK) could not. ( D ) Effects of the MAPK signaling inhibitors on the PCN033-induced upregulation of Snail-1. Selective ERK1/2 inhibitor U0126 could completely block the PCN033-induced upregulation of Snail-1. ( E – F ) Snail-1 knocking-down via shRNA in hBMEC did not affect the induction of VEGFA by PCN033, while blocking VEGFA pathway significantly decreased the upregulation of Snail-1. ( G – H ) Effects of the VEGFR inhibitors on PCN033-induced activation of ERK1/2 and the densitometric analysis. ( I – J ) TLR2 agonist Pam3CSK4 induced the activation of ERK1/2 in a dose-dependent manner. ( K – L ) Pam3CSK4 dose-dependently induced the upregulation of Snail-1 and VEGFA in hBMEC. Results are expressed as mean ± SD from three independent assays.

    Article Snippet: U0126, SB202190 and SP600125 were from Cayman Chemical Company (Ann Arbor, MI, USA).

    Techniques: Infection, Activation Assay, Blocking Assay, shRNA

    Leptin induces aromatase gene expression via effects on PKC and ERK1/2 Immortalized ASCs were treated for 24h with 0–100 ng/ml leptin. Following treatment, aromatase (A) activity, (B) mRNA expression and (C) promoter PII activity were examined and found to be increased in a dose-dependent manner. (D) Leptin stimulated the translocation of cytosolic PKC to the membrane. (E) Treatment of cells with PKC inhibitor calphostin (Cal.) led to the dose-dependent inhibition of the leptin-mediated increase in aromatase activity. ASCs were pre-treated with vehicle or the indicated concentrations of calphostin (Cal.) for 2h. Subsequently, cells were treated with leptin or leptin plus calphostin for 24 h. (F; top) Leptin treatment caused a transient increased in ERK1/2 phosphorylation. ASCs were treated with vehicle or 100 ng/ml leptin for the indicated times. Cell lysates were subjected to Western Blotting. (F; bottom) Treatment with MEK1/2 inhibitor PD98059 caused a dose-dependent decrease in the leptin-mediated induction of aromatase activity. ASCs were pretreated with vehicle or the indicated concentrations of PD98059 for 2h. Subsequently, the cells received vehicle, 100ng/ml leptin or leptin + 25–100 uM PD98059 for 24h. (G,H; top) Western blotting demonstrating time-dependent effects of leptin on phosphorylation of JNK (G) and p38 (H). No effect of inhibitors of JNK or p38 MAPK on aromatase activity was observed (G,H; bottom). ASCs were pretreated with indicated concentrations of SP600125 or SB202190, respectively for 2h. Subsequently, cells received vehicle, 100ng/ml leptin or leptin + the indicated concentrations of SP600125 or SB202190 for 24h. Aromatase activity is expressed as femtomoles/μg protein. Data are presented as mean ± SD, n=6. C: control; L: leptin.

    Journal: International journal of obesity (2005)

    Article Title: Leptin regulation of the p53-HIF1α/PKM2-aromatase axis in breast adipose stromal cells – a novel mechanism for the obesity-breast cancer link

    doi: 10.1038/ijo.2017.273

    Figure Lengend Snippet: Leptin induces aromatase gene expression via effects on PKC and ERK1/2 Immortalized ASCs were treated for 24h with 0–100 ng/ml leptin. Following treatment, aromatase (A) activity, (B) mRNA expression and (C) promoter PII activity were examined and found to be increased in a dose-dependent manner. (D) Leptin stimulated the translocation of cytosolic PKC to the membrane. (E) Treatment of cells with PKC inhibitor calphostin (Cal.) led to the dose-dependent inhibition of the leptin-mediated increase in aromatase activity. ASCs were pre-treated with vehicle or the indicated concentrations of calphostin (Cal.) for 2h. Subsequently, cells were treated with leptin or leptin plus calphostin for 24 h. (F; top) Leptin treatment caused a transient increased in ERK1/2 phosphorylation. ASCs were treated with vehicle or 100 ng/ml leptin for the indicated times. Cell lysates were subjected to Western Blotting. (F; bottom) Treatment with MEK1/2 inhibitor PD98059 caused a dose-dependent decrease in the leptin-mediated induction of aromatase activity. ASCs were pretreated with vehicle or the indicated concentrations of PD98059 for 2h. Subsequently, the cells received vehicle, 100ng/ml leptin or leptin + 25–100 uM PD98059 for 24h. (G,H; top) Western blotting demonstrating time-dependent effects of leptin on phosphorylation of JNK (G) and p38 (H). No effect of inhibitors of JNK or p38 MAPK on aromatase activity was observed (G,H; bottom). ASCs were pretreated with indicated concentrations of SP600125 or SB202190, respectively for 2h. Subsequently, cells received vehicle, 100ng/ml leptin or leptin + the indicated concentrations of SP600125 or SB202190 for 24h. Aromatase activity is expressed as femtomoles/μg protein. Data are presented as mean ± SD, n=6. C: control; L: leptin.

    Article Snippet: SP600125, SB202190, PD98059, and 17-Allylamino-17demethoxygeldanamycin (17-AAG) were obtained from Cayman Chemicals.

    Techniques: Expressing, Activity Assay, Translocation Assay, Inhibition, Western Blot

    YC-1 prevents hypoxia-induced TF through inhibition of the p38/NF-κB pathway. ( A ) Effects of specific inhibitors of MAPKs and Akt on hypoxia-induced TF expression. A549 cells were treated with U0126 (10 μM), SP600125 (10 μM), SB202190 (10 μM), and wortmannin (0.1 μM) for 1 h, and exposed to hypoxia for 24 h. Cell lysates were subjected to Western blotting for TF. ( B , C ) YC-1 inhibits hypoxia-stimulated p38 activation. Cells pretreated with YC-1 were exposed to hypoxia for 15 min ( B ) or 2 h ( C ). Cell lysates were subjected to Western blotting for p38 and MAPKAPK2. ( D ) The effect of YC-1 on ERK activation in hypoxic conditions. A549 cells were treated as in ( B ), and the cell lysates were subjected to Western blotting for ERK. ( E ) The p38 inhibitor prevents hypoxia-induced NF-κB activation. A549 cells treated with SB202190 (10 μM) or YC-1 (50 μM) were exposed to hypoxia for 2 h. Cell lysates were subjected to Western blotting for NF-κB. ( F ) The p38 and NF-κB inhibitors prevent hypoxia-induced TF activity. A549 cells treated with SB202190 (10 μM) or Ro 106-9920 (10 μM) were exposed to hypoxia for 24 h, then the TF-dependent factor Xa generation was determined. Data are presented as mean ± SEM ( n = 3). * = p

    Journal: International Journal of Molecular Sciences

    Article Title: YC-1 Prevents Tumor-Associated Tissue Factor Expression and Procoagulant Activity in Hypoxic Conditions by Inhibiting p38/NF-κB Signaling Pathway

    doi: 10.3390/ijms20020244

    Figure Lengend Snippet: YC-1 prevents hypoxia-induced TF through inhibition of the p38/NF-κB pathway. ( A ) Effects of specific inhibitors of MAPKs and Akt on hypoxia-induced TF expression. A549 cells were treated with U0126 (10 μM), SP600125 (10 μM), SB202190 (10 μM), and wortmannin (0.1 μM) for 1 h, and exposed to hypoxia for 24 h. Cell lysates were subjected to Western blotting for TF. ( B , C ) YC-1 inhibits hypoxia-stimulated p38 activation. Cells pretreated with YC-1 were exposed to hypoxia for 15 min ( B ) or 2 h ( C ). Cell lysates were subjected to Western blotting for p38 and MAPKAPK2. ( D ) The effect of YC-1 on ERK activation in hypoxic conditions. A549 cells were treated as in ( B ), and the cell lysates were subjected to Western blotting for ERK. ( E ) The p38 inhibitor prevents hypoxia-induced NF-κB activation. A549 cells treated with SB202190 (10 μM) or YC-1 (50 μM) were exposed to hypoxia for 2 h. Cell lysates were subjected to Western blotting for NF-κB. ( F ) The p38 and NF-κB inhibitors prevent hypoxia-induced TF activity. A549 cells treated with SB202190 (10 μM) or Ro 106-9920 (10 μM) were exposed to hypoxia for 24 h, then the TF-dependent factor Xa generation was determined. Data are presented as mean ± SEM ( n = 3). * = p

    Article Snippet: The extracellular regulated MAP kinase (ERK) inhibitor U0126, p38 MAP kinases inhibitor SB202190, c-Jun N-terminal kinases (JNK) inhibitor SP600125, HIF-1α inhibitor CAY10585, p38 activator anisomycin, and phosphatidylinositol-3-kinases (PI3K) inhibitor wortmannin were purchased from Cayman Chemical (Ann Arbor, MI, USA).

    Techniques: Inhibition, Expressing, Western Blot, Activation Assay, Activity Assay