DNA damage, death receptor activation and reactive oxygen species contribute to ultraviolet radiation-induced apoptosis in an essential and independent way

被引:209
作者
Kulms, D [1 ]
Zeise, E [1 ]
Pöppelmann, B [1 ]
Schwarz, T [1 ]
机构
[1] Univ Munster, Dept Dermatol, Ludwig Boltzmann Inst Cell Biol & Immunobiol Skin, D-48149 Munster, Germany
关键词
apoptosis; cytochrome c; DNA damage; reactive oxygen species; UV radiation;
D O I
10.1038/sj.onc.1205743
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nuclear DNA damage and death receptor (CD95) activation by ultraviolet-B radiation (UVB) play a major role in UVB-induced apoptosis. Removal of DNA damage combined with inhibition of death receptor activation resulted in pronounced but not complete suppression of apoptosis, indicating that a third independent pathway is involved. Since reactive oxygen species (ROS) cause apoptosis and are induced by UVB, the radical scavenger pyrrolidene-dithiocarbamate (PDTC) was used. PDTC prevented UVB-induced apoptosis partially, H2O2-induced cell death largely, but not CD95-mediated apoptosis. The same was observed for cytochrome c release from mitochondria, another important event during apoptosis. The proapoptotic protein Bid was cleaved upon exposure to UVB or to agonistic anti-CD95-antibodies, but not to H2O2, indicating that H2O2 uses a different pathway. The fact that PDTC neither inhibited CD95-mediated apoptosis nor affected UV-induced DNA damage indicated that ROS generated during UVB irradiation may directly trigger mitochondrial cytochrome c release, thereby contributing to apoptosis. Accordingly, complete inhibition of apoptosis was observed when in addition to DNA damage removal via photoreactivation and blockade of CD95 signaling by caspase-8 inhibitor zIETD, PDTC was added before UVB exposure. This indicates that DNA damage, death receptor activation and ROS formation contribute to UVB-induced apoptosis in an essential and independent way.
引用
收藏
页码:5844 / 5851
页数:8
相关论文
共 45 条
[1]   Ultraviolet light induces apoptosis via direct activation of CD95 (Fas/APO-1) independently of its ligand CD95L [J].
Aragane, Y ;
Kulms, D ;
Metze, D ;
Wilkes, G ;
Pöppelmann, B ;
Luger, TA ;
Schwarz, T .
JOURNAL OF CELL BIOLOGY, 1998, 140 (01) :171-182
[2]  
Black HS, 2001, CURR PROBL DERMATOL, V29, P140
[3]   POTENTIAL INVOLVEMENT OF FREE-RADICAL REACTIONS IN ULTRAVIOLET LIGHT-MEDIATED CUTANEOUS DAMAGE [J].
BLACK, HS .
PHOTOCHEMISTRY AND PHOTOBIOLOGY, 1987, 46 (02) :213-221
[4]   A NOVEL PROTEIN THAT INTERACTS WITH THE DEATH DOMAIN OF FAS/APO1 CONTAINS A SEQUENCE MOTIF RELATED TO THE DEATH DOMAIN [J].
BOLDIN, MP ;
VARFOLOMEEV, EE ;
PANCER, Z ;
METT, IL ;
CAMONIS, JH ;
WALLACH, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (14) :7795-7798
[5]   OXIDATIVE DAMAGE TO PROTEINS AND LIPIDS OF CNS MYELIN PRODUCED BY IN-VITRO GENERATED REACTIVE OXYGEN SPECIES [J].
BONGARZONE, ER ;
PASQUINI, JM ;
SOTO, EF .
JOURNAL OF NEUROSCIENCE RESEARCH, 1995, 41 (02) :213-221
[6]   REDOX REGULATION OF PROGRAMMED CELL-DEATH IN LYMPHOCYTES - INVITED COMMENTARY [J].
BUTTKE, TM ;
SANDSTROM, PA .
FREE RADICAL RESEARCH, 1995, 22 (05) :389-397
[7]   Mitochondrial free radical generation, oxidative stress, and aging [J].
Cadenas, E ;
Davies, KJA .
FREE RADICAL BIOLOGY AND MEDICINE, 2000, 29 (3-4) :222-230
[8]  
Chinnaiyan AM, 1996, J BIOL CHEM, V271, P4961
[9]   Molecular mechanism of nucleotide excision repair [J].
de Laat, WL ;
Jaspers, NGJ ;
Hoeijmakers, JHJ .
GENES & DEVELOPMENT, 1999, 13 (07) :768-785
[10]  
DEKOK TMCM, 1994, CARCINOGENESIS, V15, P1399, DOI 10.1093/carcin/15.7.1399