Proteomic Analysis of Salt-Induced Changes in Protein Expression in PPARα Null Mice

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DOI: 10.4236/pp.2014.511111    2,241 Downloads   2,434 Views  

ABSTRACT

PPARs are ligand-activated nuclear transcription factors that regulate β-oxidation of fatty acids in the cardiovascular system and PPARα isoform is a putative target for regulation of cardiovascular function. High salt diet is an injurious stimulus to cardiovascular function but its effect on PPARα and PPARα–associated profile of proteins is unknown. Quantitative proteomics involving a two-dimensional electrophoresis (2D-DIGE) followed by LC-MS/MS technology was used to characterize the changes in protein expression profile in the kidney, heart, and blood vessels from PPARα null (KO) and wild type (WT) mice placed on normal (0.3%, NS) or high salt (4% NaCl, HS) diet. Initial biological variation analysis using DeCyder software (v. 6.0) revealed the presence of 20 upregulated proteins and 9 proteins that are downregulated in the kidney, aorta, and heart tissues from KO and WT mice. A multimodality comparison of the differentially expressed proteins showing ≥ 1.5-fold change, ≥20% appearance at P ≤ 0.05 between strains (WT vs KO) and treatment (NS vs HS) revealed that HS diet affected 20 proteins in WT mice and 17 proteins in KO mice. However, 9 proteins were altered between WT and KO placed on NS and 7 proteins were altered by HS between WT and KO mice. The identified proteins include but not limited to those involved in fatty acid oxidation (FAO), mitochondrial electron transport chain, amino acid metabolism, stress response, DNA synthesis, and programmed cell death. HS diet led to upregulation of FAO enzymes viz: acyl-coenzyme A dehydrogenase, transketolase, and electron-transferring-flavoprotein dehydrogenase to different extents in WT and KO mice. These data showed differential and protein-specific responses to HS diet in PPARα WT and KO mice that probably reflect the functional capacities of PPARα as a means to limiting any salt-induced injury to the heart, kidney, and blood vessels.

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Obih, P. and Oyekan, A. (2014) Proteomic Analysis of Salt-Induced Changes in Protein Expression in PPARα Null Mice. Pharmacology & Pharmacy, 5, 996-1005. doi: 10.4236/pp.2014.511111.

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