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10.1002/jcp.25709

http://scihub22266oqcxt.onion/10.1002/jcp.25709
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27925186!ä!27925186

suck abstract from ncbi


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pmid27925186      J+Cell+Physiol 2017 ; 232 (10): 2841-2850
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  • Up-Regulation of Transient Receptor Potential Melastatin 6 Channel Expression by Tumor Necrosis Factor-alpha in the Presence of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor #MMPMID27925186
  • Furukawa C; Fujii N; Manabe A; Matsunaga T; Endo S; Hasegawa H; Ito Y; Yamaguchi M; Yamazaki Y; Ikari A
  • J Cell Physiol 2017[Oct]; 232 (10): 2841-2850 PMID27925186show ga
  • Anti-epidermal growth factor receptor (EGFR) drugs such as erlotinib and gefitinib cause a side effect of hypomagnesemia, but chemotherapy to treat this has not yet been developed. The transient receptor potential melastatin 6 (TRPM6) channel is involved in the reabsorption of Mg(2+) in the renal tubule. We reported previously that the expression of TRPM6 is up-regulated by epidermal growth factor (EGF) in renal tubular epithelial NRK-52E and HEK293 cells. EGF-induced elevation of TRPM6 expression was inhibited by erlotinib, gefitinib, and lapatinib. We found that tumor necrosis factor-alpha (TNF-alpha) increases TRPM6 expression in the presence of erlotinib. Therefore, we investigated what molecules are involved in the up-regulation of TRPM6 expression by TNF-alpha. EGF increased the levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (p-ERK1/2), which were inhibited by erlotinib. TNF-alpha did not change p-ERK1/2 levels, but increased the phosphorylation and nuclear localization of nuclear factor-kappaB (NF-kappaB), which were blocked by the NF-kappaB inhibitors BAY 11-7082 and pyrrolidinedithiocarbamate ammonium. Similarly, luciferase reporter activity of human TRPM6 was increased by TNF-alpha, which was blocked by NF-kappaB inhibitors, and was inhibited by a mutation in the kappaB-binding site in the proximal region of the TRPM6 promoter. A chromatin immunoprecipitation assay revealed that NF-kappaB binds to the kappaB-binding site, which was blocked by NF-kappaB inhibitors. In the presence of erlotinib, TNF-alpha increased Mg(2+) influx, which was blocked by NF-kappaB inhibitors. These results suggest that TNF-alpha reverses the reduction in Mg(2+) reabsorption caused by anti-EGFR drugs. J. Cell. Physiol. 232: 2841-2850, 2017. (c) 2016 Wiley Periodicals, Inc.
  • |Animals[MESH]
  • |Binding Sites[MESH]
  • |Epidermal Growth Factor/pharmacology[MESH]
  • |ErbB Receptors/*antagonists & inhibitors/metabolism[MESH]
  • |Erlotinib Hydrochloride/*toxicity[MESH]
  • |Extracellular Signal-Regulated MAP Kinases/metabolism[MESH]
  • |Gefitinib[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |Kidney Tubules/*drug effects/metabolism/physiopathology[MESH]
  • |Lapatinib[MESH]
  • |Magnesium/*metabolism[MESH]
  • |NF-kappa B/metabolism[MESH]
  • |Phosphorylation[MESH]
  • |Promoter Regions, Genetic[MESH]
  • |Protein Binding[MESH]
  • |Protein Kinase Inhibitors/*toxicity[MESH]
  • |Quinazolines/toxicity[MESH]
  • |Rats[MESH]
  • |Renal Reabsorption/*drug effects[MESH]
  • |TRPM Cation Channels/*drug effects/metabolism[MESH]
  • |Time Factors[MESH]
  • |Transfection[MESH]
  • |Tumor Necrosis Factor-alpha/*pharmacology[MESH]


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