Docosahexaenoic acid enhances iron uptake by modulating iron transporters and accelerates apoptotic death in PC12 cells.
The effect of docosahexaenoic acid (DHA; 22:6 n-3) on Fe(2+)-mediated and/or H(2)O(2)-mediated oxidative stress (OS) was investigated in a PC12 pheochromocytoma cell line in the presence or absence of 50 ng/ml nerve growth factor (NGF). DHA-supplemented cells showed enhanced Fe(2+)-induced cell damage as evident by increased lipid peroxides formation (10-fold) and reduced neutral red (NR) dye uptake in a NGF-independent fashion. DHA caused a nearly 10-fold increase in free iron uptake in NGF-treated cells and doubled iron uptake in nondifferentiated cells. DHA-enrichment induced an elevation in the transferrin receptor protein in the nondifferentiated cells whereas NGF-treatment led to a substantial increase in the ubiquitous divalent metal ion transporter 1 (DMT-1) as detected by mRNA levels using qRT-PCR. The mechanism of action of DHA to accelerate cell death may be associated with the externalization of amino-phosphoglycerides (PG) species of which, increased ethanolamine plasmalogen levels, may be essential for cell rescue as noted in NGF-treated PC12 cells.
Schonfeld
Eldi
E
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, 76100, Israel.
Yasharel
Ilanit
I
Yavin
Ephraim
E
Brand
Annette
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016718:Arachidonic Acid / Q000494:pharmacology; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002855:Chromatography, Thin Layer; D003470:Culture Media; D004247:DNA / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D007501:Iron / Q000032:analysis / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D000099236:Solute Carrier Family 11, Member 2
D016718:Arachidonic Acid; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D003470:Culture Media; D004247:DNA; D004281:Docosahexaenoic Acids; D005231:Fatty Acids, Unsaturated; D007501:Iron; D009414:Nerve Growth Factors; D011453:Prostaglandins; D017392:Thiobarbituric Acid Reactive Substances; D000099236:Solute Carrier Family 11, Member 2