Reactive oxygen species-producing site in radiation-induced apoptosis of human peripheral T cells: involvement of lysosomal membrane destabilization.
In our previous studies, we have partly elucidated the mechanism of radiation-induced apoptosis of human peripheral T cells. The exact site of the ROS (reactive oxygen species) formation induced by irradiation has been so far unknown. Therefore, in this study, we investigated the site of ROS formation by utilizing MitoCapture, H2DCFDA (succinimidyl ester of dichlorodihydrofluorescein diacetate), DAPI, and Lysosensor. Our results showed that ROS formation apparently originated in the mitochondria and/or lysosomes instead of in the nuclei of irradiated T cells. Moreover, lysosomal swelling and deformity, possibly revealing lysosomal membrane instability, were observed at 1 h after 5 Gy irradiation of T cells. At 4 h after irradiation of 5 Gy, increase of fluorescence around the lysosomes, possibly revealing lysosomal rupture, was seen. Based on the above results, we concluded the possible existence of a new apoptotic cascade involving early lysosomal membrane destabilization in radiation-induced apoptosis of human peripheral T cells. Therefore, possible involvement of lysosomal protease leakage caused by hydroxyl radical formation in lysosomes (possibly resulting in mitochondrial membrane dysfunction) is considered to play an important role in radiation-induced T cell apoptosis.
Ogawa
Yasuhiro
Y
Department of Radiology, Kochi Medical School, Kochi 783-8505, Japan. ogaway@kochi-ms.ac.jp
Kobayashi
Toshihiro
T
Nishioka
Akihito
A
Kariya
Shinji
S
Ohnishi
Takenao
T
Hamasato
Shinji
S
Seguchi
Harumichi
H
Yoshida
Shoji
S
D017209:Apoptosis / Q000528:radiation effects*; D006801:Humans; D007425:Intracellular Membranes / Q000528:radiation effects; D008247:Lysosomes / Q000378:metabolism / Q000528:radiation effects*; D008928:Mitochondria / Q000378:metabolism / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism / Q000528:radiation effects*
D017382:Reactive Oxygen Species