Antidepressants upregulate messenger RNA levels of the neuroprotective enzyme superoxide dismutase (SOD1).
OBJECTIVE
To investigate the effect of amitriptyline, bupropion, doxepin or venlafaxine on the gene expression of the neuroprotective enzyme superoxide dismutase (SOD1) in a catecholamine cell in vitro model.


METHODS
Molecular study of a cultured cell line.


METHODS
Rat pheochromocytoma (PC12) cells were incubated in 1 and 10 mumol/L of various antidepressant medications for 24 or 48 hours.


METHODS
Northern blot analysis.


RESULTS
Amitriptyline up-regulated SOD1 messenger RNA in a time- and dose-dependent manner. The greatest up-regulation was following incubation with 10 mumol/L amitriptyline for 48 hours. The addition of bupropion, doxepin or venlafaxine to PC12 cell cultures also up-regulated SOD1 mRNA.


CONCLUSIONS
These findings suggest that some antidepressants have the ability to positively regulate neuroprotective genes.
Li
X M
XM
Department of Psychiatry, University of Saskatchewan, Saskatoon. lixinm@sask.usask.ca
Chlan-Fourney
J
J
Juorio
A V
AV
Bennett
V L
VL
Shrikhande
S
S
Bowen
R C
RC
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D016642:Bupropion / Q000494:pharmacology; D003511:Cyclohexanols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004316:Doxepin / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics; D051381:Rats; D013482:Superoxide Dismutase / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D000069470:Venlafaxine Hydrochloride
D000928:Antidepressive Agents; D003511:Cyclohexanols; D012333:RNA, Messenger; D016642:Bupropion; D004316:Doxepin; D000639:Amitriptyline; D000069470:Venlafaxine Hydrochloride; D013482:Superoxide Dismutase