Publikation:

Rapamycin inhibits poly(ADP-ribosyl)ation in intact cells

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Datum

2009

Autor:innen

Fahrer, Jörg
Wagner, Silvia
Königsrainer, Alfred

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http://nbn-resolving.de/urn:nbn:de:bsz:352-opus-111521
DOI (zitierfähiger Link)
https://doi.org/10.1016/j.bbrc.2009.06.022
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Open Access-Veröffentlichung
Open Access Green

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Biologie: Publikationen
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Published

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Biochemical and Biophysical Research Communications. 2009, 386(1), pp. 232-236. ISSN 0006-291X. eISSN 1090-2104. Available under: doi: 10.1016/j.bbrc.2009.06.022

Zusammenfassung

Rapamycin is an immunosuppressive drug, which inhibits the mammalian target of rapamycin (mTOR) kinase activity inducing changes in cell proliferation. Synthesis of poly(ADP-ribose) (PAR) is an immediate cellular response to genotoxic stress catalyzed mostly by poly(ADP-ribose) polymerase 1 (PARP-1), which is also controlled by signaling pathways. Therefore, we investigated whether rapamycin affects PAR production. Strikingly, rapamycin inhibited PAR synthesis in living fibroblasts in a dose-dependent manner as monitored by immunofluorescence. PARP-1 activity was then assayed in vitro, revealing that down-regulation of cellular PAR production by rapamycin was apparently not due to competitive PARP-1 inhibition. Further studies showed that rapamycin did not influence the cellular NAD pool and the activation of PARP-1 in extracts of pretreated fibroblasts. Collectively, our data suggest that inhibition of cellular PAR synthesis by rapamycin is mediated by formation of a detergent-sensitive complex in living cells, and that rapamycin may have a potential as therapeutic PARP inhibitor.

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

Rapamycin, mTOR, Poly(ADP-ribosyl)ation, PARP inhibitor, Fibroblasts

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ISO 690FAHRER, Jörg, Silvia WAGNER, Alexander BÜRKLE, Alfred KÖNIGSRAINER, 2009. Rapamycin inhibits poly(ADP-ribosyl)ation in intact cells. In: Biochemical and Biophysical Research Communications. 2009, 386(1), pp. 232-236. ISSN 0006-291X. eISSN 1090-2104. Available under: doi: 10.1016/j.bbrc.2009.06.022
BibTex
@article{Fahrer2009Rapam-1115,
  year={2009},
  doi={10.1016/j.bbrc.2009.06.022},
  title={Rapamycin inhibits poly(ADP-ribosyl)ation in intact cells},
  number={1},
  volume={386},
  issn={0006-291X},
  journal={Biochemical and Biophysical Research Communications},
  pages={232--236},
  author={Fahrer, Jörg and Wagner, Silvia and Bürkle, Alexander and Königsrainer, Alfred}
}
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