PKCζ protects against UV-C-induced apoptosis by inhibiting acid sphingomyelinase-dependent ceramide production

被引:18
作者
Charruyer, Alexandra
Jean, Christine
Colomba, Audrey
Jaffrezou, Jean-Pierre
Quillet-Mary, Anne
Laurent, Guy
Bezombes, Christine [1 ]
机构
[1] INSERM, U563, Ctr Physiopathol Toulouse Purpan, F-31300 Toulouse, France
[2] Univ Toulouse 3, F-31400 Toulouse, France
[3] CHU Toulouse, Hop Purpan, Serv Hematol, F-31300 Toulouse, France
关键词
acid sphingomyelinase; antioxidant defence; protein kinase C zeta (PKC zeta); raft; thioredoxin peroxidase; UV-C;
D O I
10.1042/BJ20061528
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
In a recent study, we described that UV-C irradiation resulted in redox-dependent activation and relocalization of A-SMase (acid sphingomyelinase) to the external surface of raft membrane microdomains, hydrolysis of SM (sphingomyelin) associated with the plasma membrane outer leaflet, ceramide generation and apoptosis. In the present study, we have investigated the influence of PKC zeta (protein kinase C zeta), an atypical form of PKC on this pathway. This study shows that PKC zeta overexpression resulted in the abrogation of UV-C-induced A-SMase translocation and activation into the raft microdomains, lack of ceramide generation and apoptosis inhibition. Moreover, PKC zeta overexpression resulted in a decrease in UV-C-induced ROS (reactive oxygen species) production, which correlated with increased gene expression level of various antioxidant enzymes, including TRx (thioredoxin), TR (thioredoxin reductase) 1, TR2 and peroxiredoxin 1/TPx2 (thioredoxin peroxidase 2). Importantly, enforced TPx2 gene expression inhibited UV-C-induced A-SMase translocation. Finally, PKC zeta inhibition led to a significant reduction in TPx2 protein expression. Altogether, these results suggest that PKC zeta interferes with the UV-activated sphingolipid signalling pathway by regulating the TRx system. These findings may have important consequences for UV-induced carcinogenesis and resistance to phototherapy.
引用
收藏
页码:77 / 83
页数:7
相关论文
共 29 条
[21]   Overexpression of the atypical protein kinase C ξ reduces topoisomerase II catalytic activity, cleavable complexes formation, and drug-induced cytotoxicity in monocytic U937 leukemia cells [J].
Plo, I ;
Hernandez, H ;
Kohlhagen, G ;
Lautier, D ;
Pommier, Y ;
Laurent, G .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (35) :31407-31415
[22]   Peroxiredoxins: A historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling [J].
Rhee, SG ;
Chae, HZ ;
Kim, K .
FREE RADICAL BIOLOGY AND MEDICINE, 2005, 38 (12) :1543-1552
[23]   Caspase-dependent and -independent activation of acid sphingomyelinase signaling [J].
Rotolo, JA ;
Zhang, JJ ;
Donepudi, M ;
Lee, H ;
Fuks, Z ;
Kolesnick, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (28) :26425-26434
[24]   ULTRAVIOLET-RADIATION RAPIDLY INDUCES TYROSINE PHOSPHORYLATION AND CALCIUM SIGNALING IN LYMPHOCYTES [J].
SCHIEVEN, GL ;
KIRIHARA, JM ;
GILLILAND, LK ;
UCKUN, FM ;
LEDBETTER, JA .
MOLECULAR BIOLOGY OF THE CELL, 1993, 4 (05) :523-530
[25]   MEASUREMENT OF PROTEIN USING BICINCHONINIC ACID [J].
SMITH, PK ;
KROHN, RI ;
HERMANSON, GT ;
MALLIA, AK ;
GARTNER, FH ;
PROVENZANO, MD ;
FUJIMOTO, EK ;
GOEKE, NM ;
OLSON, BJ ;
KLENK, DC .
ANALYTICAL BIOCHEMISTRY, 1985, 150 (01) :76-85
[26]  
SMITH PK, 1987, ANAL BIOCHEM, V163, P279
[27]   The lipid raft microdomain-associated protein reggie-1/flotillin-2 is expressed in human B cells and localized at the plasma membrane and centrosome in PBMCs [J].
Solomon, S ;
Masilamani, M ;
Rajendran, L ;
Bastmeyer, M ;
Stuermer, CAO ;
Illges, H .
IMMUNOBIOLOGY, 2002, 205 (01) :108-119
[28]   Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis [J].
Verheij, M ;
Bose, R ;
Lin, XH ;
Yao, B ;
Jarvis, WD ;
Grant, S ;
Birrer, MJ ;
Szabo, E ;
Zon, LI ;
Kyriakis, JM ;
HaimovitzFriedman, A ;
Fuks, Z ;
Kolesnick, RN .
NATURE, 1996, 380 (6569) :75-79
[29]  
WAYS DK, 1994, CELL GROWTH DIFFER, V5, P1195