Inhibitory effect of polyunsaturated fatty acids on apoptosis induced by etoposide, okadaic acid and AraC in Neuro2a cells.
Neuronal apoptosis is involved in neurodegenerative diseases such as Alzheimer's disease and Parkinson.s disease. An efficient means of preventing it remains to be found. Some n-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA, 22 : 6n-3) and eicosapentaenoic acid (EPA, 20 : 5n-3) have been reported to be protective against the neuronal apoptosis and neuronal degeneration seen after spinal cord injury (SCI) [1]. However, it is unclear which kinds of PUFAs have the most potent ability to inhibit neuronal apoptosis and whether the simultaneous treatment of PUFAs inhibits the apoptosis. In the present study, we compared the abilities of various n-3- and n-6- PUFAs to inhibit the apoptosis induced after the administration of different apoptotic inducers, etoposide, okadaic acid, and AraC, in mouse neuroblastoma cells (Neuro2a). Preincubation with DHA (22 : 6n-3), eicosapentaenoic acid (EPA, 20 : 5n-3), alpha-linolenic acid (alpha-LNA, 18 : 3n-3), linoleic acid (LA, 18 : 2n-6), arachidonic acid (AA, 20 : 4n-3), and gamma-linolenic acid (gamma-LNA, 18 : 3n-6) significantly inhibited caspase-3 activity and LDH leakage but simultaneous treatment with the PUFAs had no effect on the apoptosis of Neuro2a cells. There were no significant differences of the anti-apoptotic eff ect among the PUFAs. These results suggest that PUFAs may not be effective for inhibiting neuronal cell death after acute and chronic neurodegenerative disorders. However, dietary supplementation with PUFAs may be beneficial as a potential means to delay the onset of the diseases and/or their rate of progression.
Wu
Yumei
Y
Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Tada
Mikiro
M
Takahata
Kyota
K
Tomizawa
Kazuhito
K
Matsui
Hideki
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D045744:Cell Line, Tumor; D003561:Cytarabine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology* / Q000502:physiology*; D051379:Mice; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects*; D019319:Okadaic Acid / Q000494:pharmacology
D005231:Fatty Acids, Unsaturated; D003561:Cytarabine; D019319:Okadaic Acid; D005047:Etoposide