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• W2550841963 abstract "Infantile Refsum disease (IRD), a peroxisomal disease with defective phytanic acid oxidation, causes neurological impairment and development delay. Insulin-like growth factor-1 (IGF-1) regulates child development and to understand molecular mechanism(s) of IRD, we examined the effect of phytanic acid (PA) on IGF-1 activity. Bromodeoxyuridine (BrdU) incorporation was measured in rat aortic smooth muscle cell (SMC) cultures following treatment with fetal bovine serum (FBS), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) or IGF-1 in the absence or presence of PA. Gene expression and protein contents of IGF-1 receptor (IGF-1R) and PDGF receptor (PDGFR) were examined using quantitative PCR and western blotting. PA inhibited mitogenic activities of FBS, PDGF and IGF-1 with more pronounced effect on IGF-1-induced bromodeoxyuridine (BrdU) incorporation. Palmitic acid or lignoceric acids did not inhibit IGF-1 activity. PA had no effect on PDGFR mRNA/protein levels but markedly increased IGF-1R mRNA levels. PA and nitric oxide (NO) markedly decreased IGF-1R protein. L-NAME, a NO synthase inhibitor and DAPT, a γ-secretase inhibitor, alleviated PA-induced decrease in IGF-1R protein. Both PA and NO donor increased γ-secretase activity which was alleviated by L-NAME. This study demonstrates that PA attenuates IGF-1 activity possibly through IGF-1R impairment and NO-mediated modulation of γ-secretase activity." @default.
• W2550841963 created "2016-11-30" @default.
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• W2550841963 date "2016-11-25" @default.
• W2550841963 modified "2023-09-23" @default.
• W2550841963 title "Phytanic acid attenuates insulin-like growth factor-1 activity via nitric oxide-mediated γ-secretase activation in rat aortic smooth muscle cells: possible implications for pathogenesis of infantile Refsum disease" @default.
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• W2550841963 doi "https://doi.org/10.1038/pr.2016.258" @default.
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