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Modulation of Apoptosis Induced by Tricyclic Antidepressants in Human Peripheral Lymphocytes
Author(s) -
Xia Zhenlei,
DePierre Joseph W.,
Nässberger Lennart
Publication year - 1998
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/(sici)1099-0461(1998)12:2<115::aid-jbt6>3.0.co;2-o
Subject(s) - apoptosis , aurintricarboxylic acid , cycloheximide , glutathione , pharmacology , tricyclic , chemistry , biology , microbiology and biotechnology , biochemistry , programmed cell death , protein biosynthesis , enzyme
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 interlukin‐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. © 1997 John Wiley & Sons, Inc. J Biochem Toxicol 12: 115–123, 1998