UV irradiation inhibits ABC transporters via generation of ADP-ribose by concerted action of poly(ADP-ribose) polymerase-1 and glycohydrolase.
Cell Death Differ
; 11(3): 314-20, 2004 Mar.
Article
in En
| MEDLINE
| ID: mdl-14685157
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ultraviolet Rays
/
Adenosine Diphosphate Ribose
/
Poly(ADP-ribose) Polymerases
/
ATP-Binding Cassette Transporters
/
Glycoside Hydrolases
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Death Differ
Year:
2004
Document type:
Article
Affiliation country:
Germany