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10.1038/aps.2015.114

http://scihub22266oqcxt.onion/10.1038/aps.2015.114
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suck abstract from ncbi


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pmid26775661
      Acta+Pharmacol+Sin 2016 ; 37 (2 ): 235-45
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  • Emodin ameliorates cisplatin-induced apoptosis of rat renal tubular cells in vitro by activating autophagy #MMPMID26775661
  • Liu H ; Gu LB ; Tu Y ; Hu H ; Huang YR ; Sun W
  • Acta Pharmacol Sin 2016[Feb]; 37 (2 ): 235-45 PMID26775661 show ga
  • AIM: A previous report shows that emodin extracted from the Chinese herbs rhubarb and giant knotweed rhizome can ameliorate the anticancer drug cisplatin-induced injury of HEK293 cells. In this study, we investigated whether and how emodin could protect renal tubular epithelial cells against cisplatin-induced nephrotoxicity in vitro. METHODS: The viability and apoptosis of normal rat renal tubular epithelial cells (NRK-52E) were detected using formazan assay and flow cytometry analysis, respectively. The expression levels of cleaved caspase-3, autophagy maker LC3 I/II, and AMPK/mTOR signaling pathway-related proteins were measured with Western blot analysis. The changes of morphology and RFP-LC3 fluorescence were observed under microscopy. RESULTS: Cisplatin (10-50 ?mol/L) dose-dependently induced cell damage and apoptosis in NRK-52E cells, whereas emodin (10 and 100 ?mol/L) significantly ameliorated cisplatin-induced cell damage, apoptosis and caspase-3 cleavage. Emodin dose-dependently increased LC3-II levels and induced RFP-LC3-containing punctate structures in NRK-52E cells. Furthermore, the protective effects of emodin were abolished by bafilomycin A1 (10 nmol/L), and mimicked by rapamycin (100 nmol/L). Moreover, emodin increased the phosphorylation of AMPK and suppressed the phosphorylation of mTOR. The AMPK inhibitor compound C (10 ?mol/L) not only abolished emodin-induced autophagy activation, but also emodin-induced anti-apoptotic effects. CONCLUSION: Emodin ameliorates cisplatin-induced apoptosis of rat renal tubular cells in vitro through modulating the AMPK/mTOR signaling pathways and activating autophagy. Emodin may have therapeutic potential for the prevention of cisplatin-induced nephrotoxicity.
  • |AMP-Activated Protein Kinases/metabolism [MESH]
  • |Animals [MESH]
  • |Antineoplastic Agents/*adverse effects [MESH]
  • |Apoptosis/drug effects [MESH]
  • |Autophagy/*drug effects [MESH]
  • |Caspase 3/metabolism [MESH]
  • |Cell Line [MESH]
  • |Cisplatin/*adverse effects [MESH]
  • |Emodin/*pharmacology [MESH]
  • |Humans [MESH]
  • |Kidney Tubules/cytology/*drug effects/metabolism/pathology [MESH]
  • |Protective Agents/*pharmacology [MESH]
  • |Protein Kinase Inhibitors/*pharmacology [MESH]
  • |Rats [MESH]
  • |Signal Transduction/drug effects [MESH]


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