Effects of antidepressants on mRNA levels of antioxidant enzymes in human monocytic U-937 cells.
Alterations of antioxidant enzyme activities have been described in a number of psychiatric disorders including major depression. Subsequently, the present study examined the effects of different types of antidepressants (desipramine, imipramine, maprotiline and mirtazapine) in different concentrations (10(-5), 10(-6) and 10(-7) M) on the mRNA levels of various enzymes of the antioxidant system, including both intracellular superoxide dismutase isoforms, glutathione peroxidase and catalase as well as several enzymes of the glutathione metabolism in monocytic U-937 cells after short- and long-term treatment (2.5 and 24 h) via RT-PCR. Results indicated mainly short-term decreases in the mRNA levels of antioxidant enzymes after treatment with these substances in all the concentrations used. In addition, after long-term treatment, significant increases in the mRNA levels were seen in the cases of Cu, Zn superoxide dismutase, gamma-glutamyl-cysteine synthetase, glutathione-S-transferase and glutathione reductase, including the impacts of all the antidepressants used in concentrations of 10(-6) M and 10(-7) M. Based on the large number of significant effects of all types of antidepressants tested on various antioxidant enzymes, we suggest that antioxidant enzymes may represent important targets in the course of antidepressive treatment.
Schmidt
Andreas Johannes
AJ
Department of Psychiatry and Psychotherapy, Philipps-University of Marburg, Rudolf-Bultmann-Str. 8, 35033 Marburg, Germany. andreasschmidt.marburg@freenet.de
Heiser
Philip
P
Hemmeter
Ulrich Michael
UM
Krieg
Jürgen-Christian
JC
Vedder
Helmut
H
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000096:biosynthesis / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D020298:U937 Cells
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D000975:Antioxidants; D002374:Catalase; D005978:Glutathione; D012333:RNA, Messenger; D017367:Selective Serotonin Reuptake Inhibitors; D013482:Superoxide Dismutase