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.
| Original language | English |
|---|---|
| Pages (from-to) | 314-20 |
| Number of pages | 7 |
| Journal | Cell Death & Differentiation |
| Volume | 11 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2004 |
Keywords
- ATP-Binding Cassette Transporters/antagonists & inhibitors
- Adenosine Diphosphate Ribose/biosynthesis
- Adenosine Triphosphate/analysis
- Animals
- Biological Transport, Active/radiation effects
- Cells, Cultured
- Fluorescent Dyes/metabolism
- Glycoside Hydrolases/genetics
- Granulocytes/cytology
- Humans
- Hydrolyzable Tannins/pharmacology
- Leukocytes, Mononuclear/cytology
- Mice
- Mice, Knockout
- Models, Biological
- Poly(ADP-ribose) Polymerases/genetics
- Temperature
- Ultraviolet Rays