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Protective effect of Docosahexaenoic acid (DHA) on lipotoxicity –induced cell death: implication of PI3K/AKT and MAPK pathways
Author(s) -
Descorbeth Magda,
Figueroa Karen Figueroa,
SerranoIllan Miguel,
De Leon Marino
Publication year - 2013
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.27.1_supplement.815.5
Subject(s) - lipotoxicity , protein kinase b , docosahexaenoic acid , pi3k/akt/mtor pathway , viability assay , apoptosis , chemistry , p38 mitogen activated protein kinases , medicine , endocrinology , mapk/erk pathway , signal transduction , biology , biochemistry , fatty acid , insulin resistance , polyunsaturated fatty acid , insulin
Overload of saturated fatty acids results in lipotoxicity and induces cell and tissue damage which has been associated with several pathologies in the nervous system. We have reported that palmitic acid (PA) overload induces Schwann cell (SC) apoptotic cell death in both euglycemic (EG) and hyperglycemic (HG) conditions. In this study, we investigated the potential protective effects of docosahexaenoic acid (DHA) on inhibiting PA‐induced lipotoxicity (PA‐LTx) in SC. PA (PA:BSA, 2:1) reduced cell viability in both EG and HG conditions at 48 hrs. However, co‐treatment with DHA stimulates cell viability to control levels by reversing apoptosis (nuclear condensation) observed in SC after PA‐LTx. Further, we examined whether PI3K/AKT, P38 and JNK pathways are involved in the protective effects of DHA treatment. We determined the levels of phosphorylated AKT, P38, and JNK proteins in SC under PA‐LTx with or without DHA co‐treatment using Western blots. We found that PA‐LTx decreased p‐AKT and increased p‐P38 and p‐JNK levels in a time‐dependent manner. Interestingly, DHA co‐treatment restored p‐AKT and p‐P38, but not p‐JNK to normal levels. Furthermore, LY294002 (20 μM and 40 μM), a PI3K/AKT pathway inhibitor, diminished the protective effect of DHA in SC under PA‐LTx in EG and HG conditions. In conclusion, our results demonstrate that DHA is able to protect SC from PA‐LTx by regulating the PI3K/AKT and P38 pathways. Founded by NIH award no. 1P20MD006988.