Abstract
Neuronal membranes contain exceptionally high concentrations of long-chain polyunsaturated fatty acids (PUFA), docosahexaenoic acid (DHA) and arachidonic acid (ARA), which are essential for neuronal development and function. Adult bone-marrow-derived mesenchymal stem cells (MSC) can be induced to possess some neuronal characteristics. Here we examined the effects of neuronal induction on the PUFA metabolism specific pathways. Differentiated cells contained ~30% less ARA than MSC. The expression of specific ARA metabolizing enzymes was upregulated, notably that of prostaglandin E2 synthase which increased more than 15-fold, concomitantly with a 3-fold increase in the concentration of PGE2 in the medium. Moreover, induced differentiation was associated with enhanced incorporation of exogenous DHA, upregulation of acyl-CoA synthases, fatty acid binding proteins, choline kinase (CK) and phosphatidylserine synthases as well as increased total cellular phospholipids (PL). These findings suggest that active ARA metabolites may be important in the differentiation process and that neuronal induction prepares the resulting cells for increased DHA incorporation through the action of specific enzymes.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Addresses: PG – pgreen{at}post.tau.ac.il, IK – innakan2009{at}gmail.com, NAA – argov.nurit{at}mail.huji.ac.il, RMS – Ronit_mesilati{at}walla.com, DO – danioffen{at}gmail.com
- Abbreviations
- ACSL
- acyl-CoA synthetase long-chain family member;
- ARA
- arachidonic acid;
- bFGF
- basic fibroblast growth factor;
- BF3
- boron trifluoride;
- BHA
- butylated hydroxyanisole;
- DAPI
- 4,6-diamidino-2-phenylindole;
- dbcAMP
- dibutyryl cyclic AMP;
- DHA
- docosahexaenoic acid;
- EGF
- epidermal growth factor;
- EPOX
- epoxygenases;
- FABP
- fatty acid binding protein;
- FAME
- fatty acid methyl ester;
- FCS
- fetal calf serum;
- GAPDH
- glyceraldehyde 3-phosphate dehydrogenase;
- IBMX
- 3-isobutyl-1-methyl-xanthine;
- LOX
- lipoxygenases;
- MSC
- mesenchymal stem cells;
- NeuN
- anti neuronal nuclei;
- NGF
- nerve growth factor;
- PL
- phospholipid;
- PUFA
- polyunsaturated fatty acids;
- PtdCho
- phosphatidylcholine;
- PtdEtn
- phosphatidylethanolamine;
- PtdSer
- phosphatidylserine;
- PtdIns
- phosphatidylinositol;
- PLA2
- phospholipase A2;
- PCA
- principal components analysis;
- PGI2
- prostacyclin;
- PG
- prostaglandin;
- PGE2
- prostaglandin E2;
- RA
- retinoic acid