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Cyclic AMP alleviates endoplasmic stress and programmed cell death induced by lipopolysaccharides in human endothelial cells

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Abstract

The possible protection provided by enhancement of the cAMP signal in the process of lipopolysaccharide (LPS)-induced endothelial cell death has been addressed, with special emphasis on the endoplasmic initiation of caspase-12-mediated apoptosis. Human umbilical vein endothelial cells were challenged with LPS to reduce viability after 12 h to less than 20% that of the control. Cell death was preceded by ultrastructural disintegration at the endoplasmic reticulum, PERK-phosphorylation, degradation of caspase-12-like protein and cleavage of caspase 9, resulting in apoptosis through the activation of caspase 3. Treatment with a cell-permeable cAMP analogue led to a dose-dependent reduction of cell death over time, mitigated endoplasmic reticulum disturbances, reduced phosphorylation of PERK, and the degradation of caspases 12, 9 and 3. The selective inhibition of caspase 9 completely supplanted the anti-apoptotic effects obtained by cAMP, while being without any influence on caspase 12 degradation. The data suggest that cAMP positively modulates early endoplasmic alterations and caspase activation in LPS-induced apoptosis.

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Authors and Affiliations

  1. Surgical Research Division, University Clinic of Surgery, Bonn, Germany

    Frank A. Schildberg, Susanne Schulz & Thomas Minor

  2. Institute of Pathology, University of Magdeburg, Magdeburg, Germany

    Frank Dombrowski

Authors
  1. Frank A. Schildberg
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  2. Susanne Schulz
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  3. Frank Dombrowski
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  4. Thomas Minor
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Correspondence to Thomas Minor.

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This study was supported in part by a grant from the Herbert Reeck Stiftung.

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Schildberg, F.A., Schulz, S., Dombrowski, F. et al. Cyclic AMP alleviates endoplasmic stress and programmed cell death induced by lipopolysaccharides in human endothelial cells. Cell Tissue Res 320, 91–98 (2005). https://doi.org/10.1007/s00441-004-1066-4

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  • DOI: https://doi.org/10.1007/s00441-004-1066-4

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