Possible contribution of apoptosis-inducing factor (AIF) and reactive oxygen species (ROS) to UVB-induced caspase-independent cell death in the T cell line Jurkat.
We analyzed the mechanism of UVB-induced cell death using the Jurkat T cell line. Apoptosis was assessed by measuring phosphatidylserine (PS) externalization, caspase activity, the decrease in mitochondrial membrane potential (Delta Psi m), nucleosomal DNA fragmentation, and morphological changes such as chromatin condensation. The mitochondrio-nuclear translocation of apoptosis-inducing factor (AIF) was evaluated by confocal laser microscopy. The cell death pattern of UVB-irradiated cells was similar to the Fas-induced cell death pattern. However, zVAD-fmk inhibited the nucleosomal fragmentation of DNA but not the externalization of PS, decrease in Delta Psi m, or mitochondrio-nuclear translocation of AIF. N-acetyl L-cysteine significantly inhibited the translocation of AIF induced by UVB. These results suggested that caspase-dependent and -independent pathways were involved in UVB-induced cell death in Jurkat cells, and the mitochondrio-nuclear translocation of AIF was associated with the latter pathway. In addition, reactive oxygen species generated by UVB might be involved in inducing the mitochondrio-nuclear translocation of AIF.
Murahashi
Hideaki
H
Hokkaido Red Cross Blood Center, Sapporo, Japan.
Azuma
Hiroshi
H
Zamzami
Naoufal
N
Furuya
Ko-Ji
KJ
Ikebuchi
Kenji
K
Yamaguchi
Miki
M
Yamada
Yoshiko
Y
Sato
Norihiro
N
Fujihara
Mitsuhiro
M
Kroemer
Guido
G
Ikeda
Hisami
H
D051033:Apoptosis Inducing Factor; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000528:radiation effects*; D002467:Cell Nucleus / Q000378:metabolism; D005420:Flavoproteins / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects; D008928:Mitochondria / Q000378:metabolism; D021381:Protein Transport / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000528:radiation effects*; D013601:T-Lymphocytes / Q000166:cytology / Q000528:radiation effects*; D014466:Ultraviolet Rays
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D020169:Caspases