Modulation of Apoptosis Induced by Tricyclic Antidepressants in Human Peripheral Lymphocytes

✍ Scribed by Zhenlei Xia; Joseph W. DePierre; Lennart Nässberger

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 225 KB
• Volume: 12
• Category: Article
• ISSN: 1095-6670
• DOI: 10.1002/(sici)1099-0461(1998)12:2<115::aid-jbt6>3.0.co;2-o

✦ Synopsis

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.