Titre du document / Document title

Terfenadine induces thymocyte apoptosis via mitochondrial pathway

Auteur(s) / Author(s)

ENOMOTO Riyo ^{(1 2)} ; KOMAI Tomoe ⁽¹⁾ ; YOSHIDA Yukari ⁽¹⁾ ; SUGAHARA Chiyoko ⁽¹⁾ ; KAWAGUCHI Emi ⁽¹⁾ ; OKAZAKI Keiko ⁽¹⁾ ; KINOSHITA Hiroki ⁽¹⁾ ; KOMATSU Hiroto ⁽³⁾ ; KONISHI Yasuo ⁽³⁾ ; LEE Eibai ^{(1 2)} ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, JAPON
⁽²⁾ High Technology Research Center Kobe Gakuin University, Ikawadani-cho, Nishi, Kobe 651-2180, JAPON
⁽³⁾ Biotechnology Research Institution, National Research Council, 6100, Royalmount Avenue, Montreal, Quebec, H4P 2R2, CANADA

Résumé / Abstract

The treatment of rat thymocytes with 10 μM 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.

Revue / Journal Title

European journal of pharmacology   ISSN 0014-2999   CODEN EJPHAZ 

Source / Source

2004, vol. 496, n^o1-3, pp. 11-21 [11 page(s) (article)] (1 p.1/4)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS  (1967) (Revue)

Mots-clés anglais / English Keywords

Inorganic element ; H1 Histamine receptor ; Antihistaminic ; Antagonist ; Potassium ; Ionic channel ; Mitochondria ; Cell death ; Apoptosis ; Thymocyte ; Terfenadine ; Fexofenadine ;

Mots-clés français / French Keywords

Elément minéral ; Récepteur histaminergique H1 ; Antihistaminique ; Antagoniste ; Potassium ; Canal ionique ; Mitochondrie ; Mort cellulaire ; Apoptose ; Thymocyte ; Terfénadine ; Fexofénadine ;

Mots-clés espagnols / Spanish Keywords

Elemento inorgánico ; Receptor histaminérgico H1 ; Antihistamínico ; Antagonista ; Potasio ; Canal iónico ; Mitocondria ; Muerte celular ; Apoptosis ; Timocito ; Terfenadina ; Fexofenadina ;

Mots-clés d'auteur / Author Keywords

Terfenadine ; Apoptosis ; Thymocyte ; Mitochondria ; Fexofenadine ; Voltage-dependent K+ channel ;

Localisation / Location

INIST-CNRS, Cote INIST : 13322, 35400011618411.0020