Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 48, Issue 12, Pages 1654-1662Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2010.03.021
Keywords
Antioxidant; Apoptosis; CHOP; Endoplasmic reticulum stress; eIF2 alpha; EUK-134; Hydrogen peroxide; Kidney; Lipotoxicity; Oxidants; Oxidative stress; Palmitic acid; Renal; Salubrinal; SP600125
Funding
- Kidney Research UK/Diabetes UK [DUK/ST2/2005]
- Commonwealth Scholarship Commission UK [SLCS-2004-304]
Ask authors/readers for more resources
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 (50-300 mu mol/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 2 alpha 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. (C) 2010 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available