UV irradiation inhibits ABC transporters via generation of ADP-ribose by concerted action of poly(ADP-ribose) polymerase-1 and glycohydrolase

被引：26
作者：
Dumitriu, IE [1 ]
Voll, RE [1 ]
Kolowos, W [1 ]
Gaipl, US [1 ]
Heyder, P [1 ]
Kalden, JR [1 ]
Herrmann, M [1 ]
机构：
[1] Univ Erlangen Nurnberg, Inst Clin Immunol, Dept Internal Med 3, D-91054 Erlangen, Germany
来源：
CELL DEATH AND DIFFERENTIATION | 2004年 / 11卷 / 03期
关键词：
ABC transporters; PARP-1; PARP-null cells; PARG;
D O I：
10.1038/sj.cdd.4401348
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：
ATP-binding cassette (ABC) transporters are involved in the transport of multiple substrates across cellular membranes, including metabolites, proteins, and drugs. Employing a functional fluorochrome export assay, we found that UVB irradiation strongly inhibits the activity of ABC transporters. Specific inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) restored the function of ABC transporters in UVB-irradiated cells, and PARP-1-deficient cells did not undergo UVB-induced membrane transport inhibition. These data suggest that PARP-1 activation is necessary for ABC transporter functional downregulation. The hydrolysis of poly(ADP-ribose) by poly(ADP-ribose) glycohydrolase (PARG) was also required, since specific PARG inhibitors, which limit the production of ADP-ribose molecules, restored the function of ABC transporters. Furthermore, ADP-ribose molecules potently inhibited the activity of the ABC transporter P-glycoprotein. Hence, poly(ADP-ribose) metabolism appears to play a novel role in the regulation of ABC transporters.
引用
收藏
页码：314 / 320
页数：7
相关论文
共 41 条
[31]   Engulfment of apoptotic cells involves the redistribution of membrane phosphatidylserine on phagocyte and prey [J].
Marguet, D ;
Luciani, MF ;
Moynault, A ;
Williamson, P ;
Chimini, G .
NATURE CELL BIOLOGY, 1999, 1 (07) :454-456
[32]   PABC11 (also known as MOAT-C and MRP5), a member of the ABC family of proteins, has anion transporter activity but does not confer multidrug resistance when overexpressed in human embryonic kidney 293 cells [J].
McAleer, MA ;
Breen, MA ;
White, NL ;
Matthews, N .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (33) :23541-23548
[33]   In vivo efficacy of XR9051, a potent modulator of P-glycoprotein mediated multidrug resistance [J].
Mistry, P ;
Plumb, J ;
Eccles, S ;
Watson, S ;
Dale, I ;
Ryder, H ;
Box, G ;
Charlton, P ;
Templeton, D ;
Bevan, PB .
BRITISH JOURNAL OF CANCER, 1999, 79 (11-12) :1672-1678
[34]   Tumor suppressor p53 binding protein 1 (53BP1) is involved in DNA damage-signaling pathways [J].
Rappold, I ;
Iwabuchi, K ;
Date, T ;
Chen, JJ .
JOURNAL OF CELL BIOLOGY, 2001, 153 (03) :613-620
[35]   Triggering noncycling hematopoietic progenitors and leukemic blasts to proliferate increases anthracycline retention and toxicity by downregulating multidrug resistance [J].
Smeets, MEP ;
Raymakers, RAP ;
Vierwinden, G ;
Pennings, AHM ;
Wessels, H ;
de Witte, T .
BLOOD, 1999, 94 (07) :2414-2423
[36]   Staurosporine inhibits phosphorylation of translational regulators linked to mTOR [J].
Tee, AR ;
Proud, CG .
CELL DEATH AND DIFFERENTIATION, 2001, 8 (08) :841-849
[37]   TNF-related apoptosis-inducing ligand-induced apoptosis of melanoma is associated with changes in mitochondrial membrane potential and perinuclear clustering of mitochondria [J].
Thomas, WD ;
Zhang, XD ;
Franco, AV ;
Nguyen, T ;
Hersey, P .
JOURNAL OF IMMUNOLOGY, 2000, 165 (10) :5612-5620
[38]   Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skin [J].
Virág, L ;
Szabó, É ;
Bakondi, E ;
Bai, P ;
Gergely, P ;
Hunyadi, J ;
Szabó, C .
EXPERIMENTAL DERMATOLOGY, 2002, 11 (03) :189-202
[39]   The therapeutic potential of poly(ADP-ribose) polymerase inhibitors [J].
Virág, L ;
Szabó, C .
PHARMACOLOGICAL REVIEWS, 2002, 54 (03) :375-429
[40]   MICE LACKING ADPRT AND POLY(ADP-RIBOSYL)ATION DEVELOP NORMALLY BUT ARE SUSCEPTIBLE TO SKIN-DISEASE [J].
WANG, ZQ ;
AUER, B ;
STINGL, L ;
BERGHAMMER, H ;
HAIDACHER, D ;
SCHWEIGER, M ;
WAGNER, EF .
GENES & DEVELOPMENT, 1995, 9 (05) :509-520
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