gw-5074 and pyrazolanthrone

gw-5074 has been researched along with pyrazolanthrone* in 1 studies

Other Studies

1 other study(ies) available for gw-5074 and pyrazolanthrone

Article	Year
Regulation of (pro)renin receptor expression by glucose-induced mitogen-activated protein kinase, nuclear factor-kappaB, and activator protein-1 signaling pathways. Endocrinology, 2010, Volume: 151, Issue:7 Renal (pro)renin receptor (PRR) expression is increased in diabetes. The exact mechanisms involved in this process are not well established. We hypothesized that high glucose up-regulates PRR through protein kinase C (PKC)-Raf-ERK and PKC-c-Jun N-terminal kinase (JNK)-c-Jun signaling pathways. Rat mesangial cells exposed to 30 mm d-glucose demonstrated significant increase in PRR mRNA and protein expression, intracellular phosphorylation of Raf-1 (Y340/341), ERK, JNK, nuclear factor-kappaB (NF-kappaB) p65 (S536) and c-Jun (S63). By chromatin immunoprecipitation assay and EMSA, high glucose induced more functional NF-kappaB and activator protein (AP)-1 dimers bound to corresponding cis-regulatory elements in the predicted PRR promoter to up-regulate PRR transcription. Conventional and novel PKC inhibitors Chelerythrine and Rottlerin, Raf-1 inhibitor GW5074, MEK1/2 inhibitor U0126, JNK inhibitor SP600125, NF-kappaB inhibitor Quinazoline, and AP-1 inhibitor Curcumin, respectively, attenuated glucose-induced PRR up-regulation. Chelerythrine and Rottlerin also inhibited glucose-induced phosphorylation of Raf-1 (Y340/341), ERK1/2, JNK, NF-kappaB p65 (S536), and c-Jun (S63). GW5074 and U0126 inhibited the phosphorylation of ERK1/2 and NF-kappaB p65 (S536). SP600125 inhibited phosphorylation of NF-kappaB p65 (S536) and c-Jun (S63). We conclude that high glucose up-regulates the expression of PRR through mechanisms dependent on both PKC-Raf-ERK and PKC-JNK-c-Jun signaling pathways. NF-kappaB and AP-1 are involved in high-glucose-induced PRR up-regulation in rat mesangial cells. Topics: Animals; Anthracenes; Butadienes; Cell Line; Chromatin Immunoprecipitation; Electrophoretic Mobility Shift Assay; Glucose; Indoles; MAP Kinase Kinase Kinases; Mesangial Cells; Mitogen-Activated Protein Kinases; NF-kappa B; Nitriles; Phenols; Phosphorylation; Promoter Regions, Genetic; Prorenin Receptor; Protein Binding; Proto-Oncogene Proteins c-raf; Rats; Receptors, Cell Surface; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Transcription Factor AP-1	2010

Article

Year

Regulation of (pro)renin receptor expression by glucose-induced mitogen-activated protein kinase, nuclear factor-kappaB, and activator protein-1 signaling pathways.

Endocrinology, 2010, Volume: 151, Issue:7

Renal (pro)renin receptor (PRR) expression is increased in diabetes. The exact mechanisms involved in this process are not well established. We hypothesized that high glucose up-regulates PRR through protein kinase C (PKC)-Raf-ERK and PKC-c-Jun N-terminal kinase (JNK)-c-Jun signaling pathways. Rat mesangial cells exposed to 30 mm d-glucose demonstrated significant increase in PRR mRNA and protein expression, intracellular phosphorylation of Raf-1 (Y340/341), ERK, JNK, nuclear factor-kappaB (NF-kappaB) p65 (S536) and c-Jun (S63). By chromatin immunoprecipitation assay and EMSA, high glucose induced more functional NF-kappaB and activator protein (AP)-1 dimers bound to corresponding cis-regulatory elements in the predicted PRR promoter to up-regulate PRR transcription. Conventional and novel PKC inhibitors Chelerythrine and Rottlerin, Raf-1 inhibitor GW5074, MEK1/2 inhibitor U0126, JNK inhibitor SP600125, NF-kappaB inhibitor Quinazoline, and AP-1 inhibitor Curcumin, respectively, attenuated glucose-induced PRR up-regulation. Chelerythrine and Rottlerin also inhibited glucose-induced phosphorylation of Raf-1 (Y340/341), ERK1/2, JNK, NF-kappaB p65 (S536), and c-Jun (S63). GW5074 and U0126 inhibited the phosphorylation of ERK1/2 and NF-kappaB p65 (S536). SP600125 inhibited phosphorylation of NF-kappaB p65 (S536) and c-Jun (S63). We conclude that high glucose up-regulates the expression of PRR through mechanisms dependent on both PKC-Raf-ERK and PKC-JNK-c-Jun signaling pathways. NF-kappaB and AP-1 are involved in high-glucose-induced PRR up-regulation in rat mesangial cells.

Topics: Animals; Anthracenes; Butadienes; Cell Line; Chromatin Immunoprecipitation; Electrophoretic Mobility Shift Assay; Glucose; Indoles; MAP Kinase Kinase Kinases; Mesangial Cells; Mitogen-Activated Protein Kinases; NF-kappa B; Nitriles; Phenols; Phosphorylation; Promoter Regions, Genetic; Prorenin Receptor; Protein Binding; Proto-Oncogene Proteins c-raf; Rats; Receptors, Cell Surface; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Transcription Factor AP-1

2010