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Effect of siRNA to PPARα in the rat kidney
Author(s) -
Newaz Mohammad,
Yousefipour Zivar,
Ranganna Kasturi,
Oyekan Adebayo
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a342-b
Subject(s) - peroxisome , peroxisome proliferator activated receptor , clofibrate , chemistry , small interfering rna , kidney , renal cortex , endocrinology , renal medulla , medicine , receptor , medulla , transfection , microbiology and biotechnology , biology , biochemistry , gene
Peroxisome proliferator activated receptor (PPAR) α, a nuclear transcription factor, regulates peroxisomal β oxidation and following activation, nitric oxide (NO) is produced. In this study, we examined the effect of siRNA on PPARα expression and β‐oxidation. 3 different PPARα siRNA sequences and scrambled siRNA were custom prepared and cloned into plasmid expression vector. Male Sprague Dawley rats were treated with plasmid DNA (siRNA; 10ƒÝg/rat, i.v) or scrambled sequence 24 hrs before treatment with clofibrate (Cf; 250 mg/kg; i.p x 3 days) or vehicle (control). Animals were sacrificed and tissues processed for biochemical and molecular analysis. Cf increased β oxidation (62±4, 86±10 and 56±8%; p<0.05) and PPARα expression in the liver, kidney cortex and medulla, respectively. siRNA blunted (58±9%; p<0.05) the increase in the renal medulla but not the cortex or the liver. Similarly, Cf increased PPARδ expression that was unchanged by siRNA. Cf increased NO excretion 2‐fold and siRNA reduced it (63±12%; p<0.01). siRNA also reduced medium chain acyl dehydrogenase (MCAD) expression in the renal medulla in control but not Cf‐treated rats . This study shows that siRNA inhibits PPARα expression and associated β‐oxidation in the renal medulla probably via NO inhibition. The increased expression of PPARδ in the presence of PPARα siRNA may restore normal β‐oxidation process via modulating MCAD.