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Endoplasmic Reticulum Stress in Diseases

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Saturated fatty acids induce endoplasmic reticulum stress in primary cardiomyocytes

Taha Haffar12 / Félix-Antoine Bérubé-Simard1 / Jean-Claude Tardif12 / Nicolas Bousette13

1Montreal Heart Institute, 5000 Belanger Street, Montreal, H1T 1C8, Canada

2Departments of Medicine, Université de Montréal

3Departments of Surgery, Université de Montréal

© 2015 Taha Haffar et al.. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. (CC BY-NC-ND 3.0)

Citation Information: Endoplasmic Reticulum Stress in Diseases. Volume 2, Issue 1, ISSN (Online) 2300-4266, DOI: 10.1515/ersc-2015-0004, March 2015

Publication History

Published Online:

This article offers supplementary material which is provided at the end of the article.


Abstract: Introduction: Diabetes is a major contributor to cardiovascular disease. There is a growing body of evidence pointing towards intra-myocellular lipid accumulation as an integral etiological factor. Here we aimed to determine the effect of two common fatty acids on lipid accumulation and cellular stress in primary cardiomyocytes.

Methods: We evaluated lipid accumulation biochemically (by triacylglyceride assay and radiolabeled fatty acid uptake assay) as well as histologically (by BODIPY 493/503 staining) in mouse and rat neonatal cardiomyocytes treated with saturated (palmitate) or mono-unsaturated (oleate) fatty acids. Endoplasmic reticulum (ER) stress was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. Cell viability was assessed by propidium iodide staining.

Results: We found that both oleate and palmitate led to significant increases in intracellular lipid in cardiomyocytes; however there were distinct differences in the qualitative nature of BODIPY staining between oleate and palmitate treated cardiomyocytes. We also show that palmitate caused significant apoptotic cell death and this was associated with ER stress. Interestingly, co-administration of oleate with palmitate abolished cell death, and ER stress. Finally, palmitate treatment caused a significant increase in ubiquitination of Grp78, a key compensatory ER chaperone.

Conclusion: Palmitate causes ER stress and apoptotic cell death in primary cardiomyocytes and this is associated with apparent differences in BODIPY staining compared to oleate treated cardiomyocytes. Importantly, the lipotoxic effects of palmitate are abolished with the co-administration of oleate.

Keywords : ER Stress; fatty acids; lipotoxicity; cardiomyocytes


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