Document Detail

Regulation of podocyte survival and endoplasmic reticulum stress by fatty acids.
MedLine Citation:
PMID:  20668104     Owner:  NLM     Status:  MEDLINE    
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.
Jonas Sieber; Maja Tamara Lindenmeyer; Kapil Kampe; Kirk Nicholas Campbell; Clemens David Cohen; Helmut Hopfer; Peter Mundel; Andreas Werner Jehle
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-07-28
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  299     ISSN:  1522-1466     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-04     Completed Date:  2010-10-26     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F821-9     Citation Subset:  IM    
Dept. of Biomedicine, Molecular Nephrology, Univ. Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
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MeSH Terms
Apoptosis / drug effects*
Caspase 3 / metabolism
Cell Survival / drug effects
Cells, Cultured
Endoplasmic Reticulum / drug effects*,  physiology
Fatty Acids, Monounsaturated / pharmacology*
Gene Silencing
Models, Animal
Oleic Acid / pharmacology*
Palmitic Acid / pharmacology*
Podocytes / cytology,  drug effects*,  metabolism
Stress, Physiological / physiology*
Transcription Factor CHOP / genetics,  metabolism
Grant Support
Reg. No./Substance:
0/Ddit3 protein, mouse; 0/Fatty Acids, Monounsaturated; 112-80-1/Oleic Acid; 147336-12-7/Transcription Factor CHOP; 209B6YPZ4I/palmitoleic acid; 57-10-3/Palmitic Acid; EC 3.4.22.-/Caspase 3

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