- |||||||||| U0126 / Promega, Zelboraf (vemurafenib) / Roche
Journal: Long glucocorticoid-induced leucine zipper regulates human thyroid cancer cell proliferation. (Pubmed Central) - Nov 28, 2019 Treatment with MAPK inhibitors led to the phosphorylation of the cAMP/response element-binding protein (CREB), and active CREB bound to the L-GILZ promoter, contributing to its transcription. We suggest that the CREB signaling pathway, frequently deregulated in thyroid tumors, is involved in L-GILZ upregulation and that L-GILZ regulates thyroid cancer cell proliferation, which may have potential in cancer treatment.
- |||||||||| U0126 / Promega
Preclinical, Journal: Microcystin-LR influences the in vitro oocyte maturation of zebrafish by activating the MAPK pathway. (Pubmed Central) - Nov 18, 2019 Moreover, the MAPK inhibitors (10 μM) were applied to explore the role of MAPK subtypes during MC-LR influencing OM and results showed that ERK inhibitor U0126 and p38 inhibitor SB203580 mitigated the effects of 100 μg/L MC-LR-induced MAPK hyper-phosphorylation and elevated GVBD in the oocytes. In conclusion, the present study indicates that microcystins disrupt the meiotic maturation by the pathway of MC-PP2A-MAPK-OM due to the phosphorylation disorder in oocytes.
- |||||||||| quercetin (LY294002) / Eli Lilly, Kuvan (sapropterin) / Merck (MSD), BioMarin, Daiichi Sankyo, U0126 / Promega
Journal: Nitric oxide: Is it the culprit for the continued expansion of keloids? (Pubmed Central) - Nov 14, 2019 In this study, we investigated the effect of NO on KDFs proliferation by Sodium Nitroprusside (SNP), an NO donor...U0126 and LY294002, inhibitors of Erk and Akt respectively, block SNP-enhanced KDFs proliferation effectively...Moreover, it decreased the expression of p, a cell cycle inhibitor. Our results reveal that SNP induced KDFs proliferation and loss contact inhibition led to pile up growth via activation of the Erk and Akt pathways, as well as a decreased expression of p. Thus, we speculate that the pathological feature of continuous expansion in keloids is caused by NO-induced KDFs sustained growth.
- |||||||||| U0126 / Promega
Journal: TGF-β1 facilitates cell-cell communication in osteocytes via connexin43- and pannexin1-dependent gap junctions. (Pubmed Central) - Nov 1, 2019 TGF-β1 increased the accumulation of Smad3 in the nuclear region (immunofluorescence assay) and promoted the enrichment of Smad3 at the binding sites of the promoters of Gja1 (Cx43) and Panx1 (ChIP assay), thereby initiating the enhanced gene expression. These results provide a deep understanding of the molecular mechanisms involved in the modulation of cell-cell communication in osteocytes induced by TGF-β1.
- |||||||||| low molecular weight dextran sulfate (ILB) / TikoMed, U0126 / Promega, SP600125 / Celgene
Preclinical, Journal, IO Biomarker: IgG plasma cells initiate changes in the protein C system in mouse ulcerative colitis through CD14+CD64+ macrophage activation. (Pubmed Central) - Oct 31, 2019 There is a possibility that the interaction between IgG plasma cells and CD14+CD64+ macrophages, as well as further secretion of cytokines from CD14+CD64+ macrophages by the formation and stimulation of IgG-IC, subsequently influence MVECs through the β-arrestin-MAPK pathway. Enhancement of PCS activity may represent a novel approach for treating UC.
- |||||||||| U0126 / Promega
Preclinical, Journal: Potent block of potassium channels by MEK inhibitor U0126 in primary cultures and brain slices. (Pubmed Central) - Oct 16, 2019 Despite the potent and reversible action of U0126 on K channels, PD98059, a structurally-unrelated MEK inhibitor, did not induce such an effect, suggesting U0126 may act independently of MEK inhibition. Together, these results raise cautions for using U0126 as a specific inhibitor for studying MEK signaling in neurons; on the other hand, further studies on the blocking mechanisms of U0126 as a potent inhibitor of K may provide useful insights into the structure-function relationship of K in general.
- |||||||||| U0126 / Promega
Knockdown of Central (Pro)Renin Receptor Attenuates Renal Injury in a High-Salt-Load CKD Rat Model (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_3782; Protocol B, U0126, Wortmannin and Losartan were used to inhibit MAPK/ERK1/2,PI3K/Akt signaling pathway, and ACE1-Ang II-AT1 axis in CKD model by continuous central administration and a high-salt diet was given for 4 weeks, respectively...Central PRR may affect renal pathology through the ACE1-Ang II-AT1 axis as well as MAPK/ERK1/2 and PI3K/Akt signaling pathways. Funding Government Support - Non-U.S.
- |||||||||| Alverix (amiloride hydrochloride) / Remedica, U0126 / Promega
Chronic Fluid Shear Stress (FSS) Induces ERK Dependent Sodium Transport in Principal Cells (PCs) (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_2849; Methods To test this, murine PCs (mpkccd) were grown on snapwells under static conditions or exposed to 0.4 dynes/cm2 of FSS for 24 hrs and amiloride sensitive Na current (Iasc) measured in an Ussing chamber...Next, we tested whether U0126, a MEK inhibitor, could recover the FSS mediated reduction in Iasc...In sham kidneys pERK co-localized with PC cells; however, in nephrectomized mice pERK chiefly co-localized with DBA and in a minority of cells localized with non-DBA stained cells of the CCD. Conclusion Chronic FSS induces ERK to stimulate ENaC dependent Na transport in vitro, and in vivo pERK is expressed primarily in PCs, suggesting ERK may play an identical role in vivo Funding Veterans Affairs Support
- |||||||||| Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
Identification of a Novel Smad Target in SGLT2-Mediated CTGF/CCN2 Expression (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_2705; Hayashida (2013) showed that glucose mediated ERK activation of LR potentiated Smad regulated transcription in mesangial cells. As MEK inhibition was able to reverse LR phosphorylation in our PTECs, our data indicates an important role for ERK in facilitating the observed glucose mediated pro-fibrotic effect.
- |||||||||| U0126 / Promega
Preclinical, Journal, IO Biomarker: Interleukin-1β Induces Apoptosis in Annulus Fibrosus Cells through the Extracellular Signal-regulated Kinase Pathway. (Pubmed Central) - Oct 13, 2019 Three experimental groups were established, including Control, IL-1β, and IL-1β+U0126 groups, respectively...Furthermore, apoptosis-related gene expression levels of B-cell lymphoma-2 associated X (Bax), caspase-3, and caspase-9 were decreased significantly compared with the IL-1β group, and the expression level of B-cell lymphoma-2 (Bcl-2) was increased significantly compared with the IL-1β group. These results suggest that IL-1β induces apoptosis in AFCs through the ERK pathway, and ERK inhibition may provide some protection against the adverse effects of IL-1β.
- |||||||||| quercetin (LY294002) / Eli Lilly, U0126 / Promega, SP600125 / Celgene
Journal: Myricetin treatment induces apoptosis in canine osteosarcoma cells by inducing DNA fragmentation, disrupting redox homeostasis, and mediating loss of mitochondrial membrane potential. (Pubmed Central) - Oct 2, 2019 Moreover, inhibition of PI3K and MAPK using LY294002, U0126, or SP600125, in addition to myricetin treatment, effectively suppressed cell proliferation compared to treatment with myricetin or each inhibitor alone. Therefore, we concluded that myricetin may be a potentially effective and less toxic therapeutic agent to prevent and control progression of canine osteosarcoma.
- |||||||||| quercetin (LY294002) / Eli Lilly, U0126 / Promega, SP600125 / Celgene
Journal: Sideroxylin (Callistemon lanceolatus) suppressed cell proliferation and increased apoptosis in ovarian cancer cells accompanied by mitochondrial dysfunction, the generation of reactive oxygen species, and an increase of lipid peroxidation. (Pubmed Central) - Sep 28, 2019 Additionally, sideroxylin activated the phosphorylation of ERK1/2, JNK, P38, and MAPK proteins and the use of LY294002, U0126, SB203580, and SP600125 to block their phosphorylation, respectively, in ES2 and OV90 cells. Collectively, the results of present study indicated that sideroxylin was a novel therapeutic agent to combat the proliferation of ovarian cancer cells through the induction of mitochondrial dysfunction and the activation of PI3 K and MAPK signal transduction.
- |||||||||| U0126 / Promega
Journal: SCF promotes the production of IL-13 via the MEK-ERK-CREB signaling pathway in mast cells. (Pubmed Central) - Sep 27, 2019 However, JSI-124 (JAK/STAT3 pathway inhibitor), Wortmannin (PI3K/Akt pathway inhibitor) and PDTC (NF-κB inhibitor) had no effect on the role of SCF promoting the P815 cells producing IL-13. Therefore, SCF signaling promotes mast cell P815 to produce IL-13, and this effect is associated with the MEK-ERK-CREB signaling pathway.
- |||||||||| U0126 / Promega
Journal, IO Biomarker: Phosphorylation of TMEM55B by Erk/MAPK regulates lysosomal positioning. (Pubmed Central) - Sep 19, 2019 Of these stimuli, Toll-like receptor ligands most strongly induce TMEM55B phosphorylation, and this is blocked by the MEK1/2 inhibitor U0126...Overexpression of TMEM55B but not TMEM55A notably enhances lamp1 clustering, with TMEM55B mutants (lacking phosphorylation sites or mimicking the phosphorylated state) exhibiting lower and higher efficacies (respectively) than wild-type TMEM55B. Collectively, results suggest that phosphorylation of TMEM55B by Erk/MAPK impacts lysosomal dynamics.
|