A phosphatidylinositol transfer protein alpha-dependent survival factor protects cultured primary neurons against serum deprivation-induced cell death.
Selective neuronal loss is a prominent feature in both acute and chronic neurological disorders. Recently, a link between neurodegeneration and a deficiency in the lipid transport protein phosphatidylinositol transfer protein alpha (PI-TPalpha) has been demonstrated. In this context it may be of importance that fibroblasts overexpressing PI-TPalpha are known to produce and secrete bioactive survival factors that protect fibroblasts against UV-induced apoptosis. In the present study it was investigated whether the conditioned medium of cells overexpressing PI-TPalpha (CMalpha) has neuroprotective effects on primary neurons in culture. We show that CMalpha is capable of protecting primary, spinal cord-derived motor neurons from serum deprivation-induced cell death. Since the conditioned medium of wild-type cells was much less effective, we infer that the neuroprotective effect of CMalpha is linked (in part) to the PI-TPalpha-dependent production of arachidonic acid metabolites. The neuroprotective activity of CMalpha is partly inhibited by suramin, a broad-spectrum antagonist of G-protein coupled receptors. Western blot analysis shows that brain cortex and spinal cord express relatively high levels of PI-TPalpha, suggesting that the survival factor may be produced in neuronal tissue. We propose that the bioactive survival factor is implicated in neuronal survival. If so, PI-TPalpha could be a promising target to be evaluated in studies on the prevention and treatment of neurological disorders.
Bunte
Hanneke
H
Bijvoet Center for Biomolecular Research, Department of Biochemistry of Lipids, Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands. h.bunte@chem.uu.nl
Schenning
Martijn
M
Sodaar
Peter
P
Bär
Dop P R
DP
Wirtz
Karel W A
KW
van Muiswinkel
Freek L
FL
Snoek
Gerry T
GT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D015870:Gene Expression / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal / Q000379:methods; D008954:Models, Biological; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects*; D049294:Phospholipid Transfer Proteins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000166:cytology; D013997:Time Factors
D016895:Culture Media, Serum-Free; D049294:Phospholipid Transfer Proteins