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Prevention of endotoxin-induced lethality, but not of liver apoptosis in Poly(ADP-ribose) polymerase-deficient mice

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Leist_Kuehnle_Prevention 201643.pdf
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1999

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Biochemical and Biophysical Research Communications. 1999, 263(2), pp. 433-438. ISSN 0006-291X. Available under: doi: 10.1006/bbrc.1999.1393

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Activation of poly-(ADP-ribose) polymerase (PARP) is often associated with cytotoxicity, but its precise role in shock-induced lethality and in different modes of tissue injury is still unknown. We took advantage of the existence of mice with a targeted deletion of the PARP gene (PARP−/−) to examine the differential sensitivity of wild-type (wt) and PARP−/− mice toward endotoxin (LPS)-induced lethality and different forms of liver damage. All PARP−/− animals survived high-dose (20 mg/kg) LPS-mediated shock, which killed 60% of wt animals. Moreover, LPS-induced necrotic liver damage was significantly reduced. In contrast, when apoptotic liver damage was induced via injection of low concentrations of LPS (30 μg/kg) into D-galactosamine-sensitized mice, or via activation of hepatic cell death receptors, PARP−/− animals were not protected. We conclude that PARP is involved in systemic LPS toxicity, while it plays a minor role in apoptotic liver damage mediated by TNF or CD95.

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570 Biowissenschaften, Biologie

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ISO 690KÜHNLE, Simone, Pierluigi NICOTERA, Albrecht WENDEL, Marcel LEIST, 1999. Prevention of endotoxin-induced lethality, but not of liver apoptosis in Poly(ADP-ribose) polymerase-deficient mice. In: Biochemical and Biophysical Research Communications. 1999, 263(2), pp. 433-438. ISSN 0006-291X. Available under: doi: 10.1006/bbrc.1999.1393
BibTex
@article{Kuhnle1999-09-24Preve-20164,
  year={1999},
  doi={10.1006/bbrc.1999.1393},
  title={Prevention of endotoxin-induced lethality, but not of liver apoptosis in Poly(ADP-ribose) polymerase-deficient mice},
  number={2},
  volume={263},
  issn={0006-291X},
  journal={Biochemical and Biophysical Research Communications},
  pages={433--438},
  author={Kühnle, Simone and Nicotera, Pierluigi and Wendel, Albrecht and Leist, Marcel}
}
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