Lipotoxicity in renal proximal tubular cells: Relationship between endoplasmic reticulum stress and oxidative stress pathways

Elias Katsoulieris, Jon G. Mabley, Mohamed Samai, Martyn A. Sharpe, Irene C. Green, Prabal K. Chatterjee

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Hyperlipidemia in the general population has been linked to the development of chronic kidney disease with both oxidative and endoplasmic reticulum stress implicated. Physiological levels (50-300μmol/L) of saturated fatty acids such as palmitic acid (PA) cause cytotoxicity in vitro. We investigated cell type- and stimulus-specific signaling pathways induced by PA in renal proximal tubular cells and whether oxidative stress leads to ER stress or vice versa and which pathways predominate in signaling for PA-induced apoptosis and necrosis. NRK-52E cells were incubated with PA or hydrogen peroxide (H2O2) combined with SP600125 which blocks c-Jun N-terminal kinase (JNK) activation; salubrinal, which maintains eukaryotic initiation factor 2α in its phosphorylated state and the antioxidant EUK-134 - a superoxide dismutase mimetic with catalase activity. We found that (i) PA causes both oxidative and ER stress leading to apoptosis which is mediated by phosphorylated JNK; (ii) oxidant-induced apoptosis generated by H2O2 involves ER stress signaling and CHOP expression; (iii) the ER stress mediated by PA is largely independent of oxidative stress; (iv) in contrast, the apoptosis produced by PA is mediated partly via oxidative stress. PA-mediated cell signaling in renal NRK-52E cells therefore differs from that identified in neuronal, hepatic and pancreatic beta cells.

Original languageEnglish (US)
Pages (from-to)1654-1662
Number of pages9
JournalFree Radical Biology and Medicine
Issue number12
StatePublished - Jun 2010


  • Antioxidant
  • Apoptosis
  • CHOP
  • EIF2α
  • Endoplasmic reticulum stress
  • EUK-134
  • Hydrogen peroxide
  • Kidney
  • Lipotoxicity
  • Oxidants
  • Oxidative stress
  • Palmitic acid
  • Renal
  • Salubrinal
  • SP600125

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


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