Saturated fatty acids induce endoplasmic reticulum stress in primary cardiomyocytes

• Autorzy: Taha Haffar , Félix-Antoine Bérubé-Simard , Jean-Claude Tardif , Nicolas Bousette
• Języki publikacji: EN

Abstrakty

EN

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.

Słowa kluczowe

EN

ER Stress; fatty acids; lipotoxicity; cardiomyocytes

• Czasopismo: Endoplasmic Reticulum Stress in Diseases
• Rocznik: 2015
• Tom: 2
• Numer: 1

Daty

otrzymano

2014-09-15

zaakceptowano

2015-02-11

online

2015-03-30

Twórcy

autor

Taha Haffar

• Montreal Heart Institute,
  5000 Belanger Street, Montreal, H1T 1C8, Canada
• Departments of Medicine,
  Université de Montréal

autor

Félix-Antoine Bérubé-Simard

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

autor

Jean-Claude Tardif

• Montreal Heart Institute,
  5000 Belanger Street, Montreal, H1T 1C8, Canada
• Departments of Medicine,
  Université de Montréal

autor

Nicolas Bousette

• Montreal Heart Institute,
  5000 Belanger Street, Montreal, H1T 1C8, Canada
• Departments of Surgery, Université de Montréal

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Identyfikatory

DOI

10.1515/ersc-2015-0004