Regulation of Podocyte Survival and Endoplasmic Reticulum Stress by Fatty Acids

Jehle, Andreas Werner. (2010) Regulation of Podocyte Survival and Endoplasmic Reticulum Stress by Fatty Acids. American journal of physiology : AJP, Vol. 299, H. 4 , F821-829.

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Official URL: http://edoc.unibas.ch/dok/A6031581

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Apoptosis of podocytes is considered critical in the pathogenesis of diabetic nephropathy (DN). Free fatty acids (FFAs) are critically involved in the pathogenesis of diabetes mellitus type 2, in particular the regulation of pancreatic β cell survival. The objectives of this study were to elucidate the role of palmitic acid, palmitoleic, and oleic acid in the regulation of podocyte cell death and endoplasmic reticulum (ER) stress. We show that palmitic acid increases podocyte cell death, both apoptosis and necrosis of podocytes, in a dose and time-dependent fashion. Palmitic acid induces podocyte ER stress, leading to an unfolded protein response as reflected by the induction of the ER chaperone immunoglobulin heavy chain binding protein (BiP) and proapoptotic C/EBP homologous protein (CHOP) transcription factor. Of note, the monounsaturated palmitoleic and oleic acid can attenuate the palmitic acid-induced upregulation of CHOP, thereby preventing cell death. Similarly, gene silencing of CHOP protects against palmitic acid-induced podocyte apoptosis. Our results offer a rationale for interventional studies aimed at testing whether dietary shifting of the FFA balance toward unsaturated FFAs can delay the progression of DN.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Molecular Nephrology (Jehle)
UniBasel Contributors:Jehle, Andreas Werner
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Physiological Society
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:19 Jul 2013 07:43
Deposited On:19 Jul 2013 07:37

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