Neuronal zinc stores are modulated by non-steroidal anti-inflammatory drugs: an optical analysis in cultured hippocampal neurons.
Zinc chelation and non-steroidal anti-inflammatory drugs (NSAIDs) have been explored as potential neuroprotective agents. However, it remains unknown whether NSAIDs and zinc chelation may converge on a similar cellular process. Using two-photon microscopy to observe hippocampal neurons labeled with a zinc-sensitive dye, we provide evidence that three chemically unrelated NSAIDs, niflumic acid, ibuprofen, and naproxen, acutely increase intracellular zinc stores from extracellular metal pools. Phospholipase A2 inhibitors triggered similar responses, suggesting that NSAIDs likely control zinc stores by their activity as cyclooxygenase inhibitors. These results provide evidence for a new link between cyclooxygenase metabolites and the mechanisms controlling neuronal zinc pools.
Love
Rachal
R
Department of Cell Biology and the Center for Neurodegenerative Disease, Emory University, 615 Michael Street, Room 446, Atlanta, GA 30322, USA.
Salazar
Gloria
G
Faundez
Victor
V
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005029:Ethylenediamines / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D005456:Fluorescent Dyes / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D018942:Macrolides / Q000494:pharmacology; D018613:Microscopy, Confocal / Q000379:methods; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009544:Niflumic Acid / Q000494:pharmacology; D010396:Penicillamine / Q000494:pharmacology; D015363:Quinolones / Q000378:metabolism; D051381:Rats; D013440:Sulfides / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors; D014105:Tosyl Compounds / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*; D015034:Zinc Oxide / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002614:Chelating Agents; D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D005029:Ethylenediamines; D005456:Fluorescent Dyes; D018942:Macrolides; D015363:Quinolones; D013440:Sulfides; D014105:Tosyl Compounds; D009544:Niflumic Acid; C040929:bafilomycin A1; D010396:Penicillamine; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine; D015034:Zinc Oxide; D000111:Acetylcysteine; C033479:sodium sulfide; C084731:zinquin