Terfenadine induces thymocyte apoptosis via mitochondrial pathway.
The treatment of rat thymocytes with 10 microM terfenadine resulted in a significant increase in DNA fragmentation. The DNA fragmentation induced by terfenadine was dependent on its concentration and incubation time. In terfenadine-treated cells, the translocation of phosphatidylserine from the inside of plasma membrane to the outside, an early event of the apoptotic process, and chromatin condensation, the morphological characterization of apoptotic cell death, were observed. Terfenadine stimulated caspase-8, -9 and -3-like activities in an incubation time-dependent manner in thymocytes. The active forms of caspase-3 and -9 were detected in the extract from terfenadine-treated cells by immunoblotting analysis using specific antibodies to caspases, but active caspase-8 was not found in this fraction. Decrease in mitochondrial membrane potential and the release of cytochrome c from mitochondria to cytosol were observed in terfenadine-treated thymocytes. These results suggest that terfenadine induces apoptosis in rat thymocytes via mitochondrial pathway.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
Riyo
R
Enomoto
Tomoe
T
Komai
Yukari
Y
Yoshida
Chiyoko
C
Sugahara
Emi
E
Kawaguchi
Keiko
K
Okazaki
Hiroki
H
Kinoshita
Hiroto
H
Komatsu
Yasuo
Y
Konishi
Eibai
E
Lee
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D016593:Terfenadine / Q000494:pharmacology*
D016593:Terfenadine