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Arachidonic acid inhibits retinoic acid‐induced neuritogenesis of human neuroblastoma SH‐SY5Y cells
Author(s) -
AMISSAH FELIX,
AYUK-TAKEM LAMBERT T.,
LAMANGO NAZARIUS S.
Publication year - 2012
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.26.1_supplement.968.1
Subject(s) - neurite , retinoic acid , arachidonic acid , polyunsaturated fatty acid , eicosapentaenoic acid , intracellular , sh sy5y , chemistry , apoptosis , viability assay , biochemistry , microbiology and biotechnology , biology , cell culture , enzyme , neuroblastoma , fatty acid , gene , in vitro , genetics
Polyisoprenylated proteins regulate intracellular processes such as cell growth, differentiation, oncogenic transformation and actin cytoskeletal organization. Recent discoveries show that polyunsaturated fatty acids (PUFAs) may be involved in neurodegenerative diseases. PUFAs such as arachidonic (AA), and eicosapentaenoic acids (EPA) induce apoptosis in cultured cells. This effect has recently been shown to correlate with the inhibition of polyisoprenylated methylated protein methyl esterase (PMPMEase). We propose that abnormally high levels of PUFAs may be deleterious to neuronal cells. Enzyme kinetics analysis with PMPMEase revealed a 2‐fold decrease in K M from 16.2 ± 1.34 to 8.60 ± 1.20 and 7.84 ± 1.02 μM in the presence of 10 μM AA or EPA, respectively. A relatively severe degenerative effect of AA on SH‐SY5Y cells was observed in the absence of 10% FBS (EC 50 of 6.2 μM). AA (2 – 10 μM) caused concentration and time‐dependent inhibition of neuritogenesis in retinoic acid (RA)‐differentiated SH‐SY5Y cells. Significant decreases in the percentage of neurite‐bearing cells and neurite lengths were observed after 24 h with 10 μM AA. These results suggest that excessive PMPMEase inhibition may extend beyond controlling cell viability to the degeneration of vulnerable cells such as neurons. Supported by NIH/NIGMS/SCORE (GM 08111‐35) & NIH/NCRR (G12 RR0 3020).