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

Fahrer, Jörg; Wagner, Silvia; Bürkle, Alexander; Königsrainer, Alfred

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

Dateien

Fahrer_opus-111521.pdfGröße: 430.99 KBDownloads: 263

Datum

2009

Autor:innen

Fahrer, Jörg

Wagner, Silvia

Bürkle, Alexander

Königsrainer, Alfred

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen 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

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.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

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

Zitieren

ISO 690

FAHRER, 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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Universitätsbibliographie

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