title: Modulation of apoptosis induced by tricyclic antidepressants in human peripheral lymphocytes.
abstract: We have recently reported that the tricyclic antidepressants (TCAs) imipramine, clomipramine, and citalopram induce apoptosis in human peripheral lymphocytes. This system is well suited for studies on the pathophysiology/physiology of apoptosis regulation. Apoptosis was determined using both DNA gel electrophoresis and flow cytometric analysis. TCA-induced apoptosis in lymphocytes was monitored in the presence of the protein synthesis inhibitor cycloheximide (CHX), the RNA synthesis inhibitor actinomycin D (Act D), the antioxidant reduced glutathione (GSH), the nuclease inhibitor aurintricarboxylic acid (ATA), the cytokine interleukin-2 (IL-2), and the immunostimulator linomide. CHX and Act D failed to prevent and actually enhanced TCA-induced apoptosis in lymphocytes, indicating that protein and RNA syntheses are not required for this process. Exogenous IL-2, GSH, and ATA protected the lymphocytes from apoptosis induced by TCAs in a dose-dependent manner, whereas linomide had no effect on TCA-induced apoptosis under our in vitro conditions. Our data demonstrate that TCA-induced apoptosis in human lymphocytes shares many common features with other stimuli-induced apoptotic processes.
authors.affiliation: Department of Biochemistry, Wallenberg Laboratory, Stockholm University, Sweden.
authors.forename: Z
authors.initials: Z
authors.lastname: Xia
authors.forename: J W
authors.initials: JW
authors.lastname: DePierre
authors.forename: L
authors.initials: L
authors.lastname: Nässberger
mesh_terms: D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D006912:Hydroxyquinolines / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D006912:Hydroxyquinolines; D007376:Interleukin-2; D003609:Dactinomycin; C045282:roquinimex; D001312:Aurintricarboxylic Acid; D003513:Cycloheximide; D005978:Glutathione