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10.1038/cddis.2017.475

http://scihub22266oqcxt.onion/10.1038/cddis.2017.475
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suck abstract from ncbi


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pmid29022917
      Cell+Death+Dis 2017 ; 8 (10 ): e3099
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  • Trehalose protects against cadmium-induced cytotoxicity in primary rat proximal tubular cells via inhibiting apoptosis and restoring autophagic flux #MMPMID29022917
  • Wang XY ; Yang H ; Wang MG ; Yang DB ; Wang ZY ; Wang L
  • Cell Death Dis 2017[Oct]; 8 (10 ): e3099 PMID29022917 show ga
  • Autophagy has an important renoprotective function and we recently found that autophagy inhibition is involved in cadmium (Cd)-induced nephrotoxicity. Here, we aimed to investigate the protective effect of trehalose (Tre), a novel autophagy activator, against Cd-induced cytotoxicity in primary rat proximal tubular (rPT) cells. First, data showed that Tre treatment significantly decreased Cd-induced apoptotic cell death of rPT cells via inhibiting caspase-dependent apoptotic pathway, evidenced by morphological analysis, flow cytometric and immunoblot assays. Also, administration with Tre protected rPT cells against Cd-induced lipid peroxidation. Inhibition of autophagic flux in Cd-exposed rPT cells was markedly restored by Tre administration, demonstrated by immunoblot analysis of autophagy marker proteins and GFP and RFP tandemly tagged LC3 method. Resultantly, Cd-induced autophagosome accumulation was obviously alleviated by Tre treatment. Meanwhile, blockage of autophagosome-lysosome fusion by Cd exposure was noticeably restored by Tre, which promoted the autophagic degradation in Cd-exposed rPT cells. Moreover, Tre treatment markedly recovered Cd-induced lysosomal alkalinization and impairment of lysosomal degradation capacity in rPT cells, demonstrating that Tre has the ability to restore Cd-impaired lysosomal function. Collectively, these findings demonstrate that Tre treatment alleviates Cd-induced cytotoxicity in rPT cells by inhibiting apoptosis and restoring autophagic flux.
  • |Animals [MESH]
  • |Apoptosis/*drug effects [MESH]
  • |Autophagosomes/physiology [MESH]
  • |Autophagy/*drug effects [MESH]
  • |Cadmium/*toxicity [MESH]
  • |Caspase 3/metabolism [MESH]
  • |Caspase 9/metabolism [MESH]
  • |Cells, Cultured [MESH]
  • |Kidney Tubules, Proximal/cytology/drug effects/*pathology [MESH]
  • |Lipid Peroxidation/drug effects [MESH]
  • |Lysosomes/physiology [MESH]
  • |Oxidative Stress/drug effects [MESH]
  • |Poly(ADP-ribose) Polymerases/metabolism [MESH]
  • |Primary Cell Culture [MESH]
  • |Protective Agents/*pharmacology [MESH]
  • |Rats [MESH]
  • |Rats, Sprague-Dawley [MESH]


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