Integrin-mediated suppression of endotoxin-induced DNA damage in lung endothelial cells is sensitive to poly(ADP-ribose) polymerase-1 gene deletion

  • Authors:
    • Hong Huang
    • Jane L. McIntosh
    • Lanyan Fang
    • Csaba Szabo
    • Dale G. Hoyt
  • View Affiliations

  • Published online on: October 1, 2003     https://doi.org/10.3892/ijmm.12.4.533
  • Pages: 533-540
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Endotoxin (LPS) is a cause of adult respiratory distress syndrome (ARDS), a disease which is preceded by acute lung injury involving the pulmonary endothelium. Experimentally, LPS causes acute DNA strand breakage in mouse lung endothelial cells (MLEC). Engagement of integrin cell adhesion receptors inhibits acute DNA breakage, which could be of use in reducing lung injury. Because integrins presumably inhibit DNA damage or activate repair, we hypothesized that the DNA-damage response protein, poly(ADP-ribose) polymerase-1 (PARP-1), regulates the protective action of integrins, as well as sensitivity to LPS. Therefore, the effect of LPS on MLEC cultured from wild-type and PARP-1 knockout mice was determined. Fluorescence microscopic measures were used to assess plasma membrane integrity, PARP activity, DNA strand breakage and DNA repair in attached cells. LPS caused a concentration-dependent increase in the permeability of wild-type MLEC. Engagement of β1 integrins with an antibody protected wild-type MLEC from this LPS-induced injury. Wild-type cells treated with the PARP-inhibitor, 3-aminobenzamide, and PARP-1 knockout MLEC were also resistant. LPS caused acute DNA breakage in both wild-type and knockout MLEC, but PARP was activated only in wild-type cells. LPS-induced DNA breakage was inhibited by 3-aminobenzamide, but not by knockout. Anti-β1 integrin antibody also inhibited the DNA breakage and PARP activation caused by LPS in wild-type MLEC. However, integrin engagement did not prevent DNA breakage in PARP-1 knockout cells, despite a similar level of β1 integrin in wild-type and knockout cells. Thus, integrin engagement, 3-aminobenzamide, and PARP-1 deletion protected MLEC from increases in membrane permeability caused by LPS. PARP-1 deletion also impaired the ability of integrin engagement to inhibit LPS-induced DNA breakage, suggesting that knockout may affect nuclear factors necessary for integrin-mediated suppression of LPS-induced DNA breakage.

Related Articles

Journal Cover

October 2003
Volume 12 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Huang H, McIntosh JL, Fang L, Szabo C and Hoyt DG: Integrin-mediated suppression of endotoxin-induced DNA damage in lung endothelial cells is sensitive to poly(ADP-ribose) polymerase-1 gene deletion. Int J Mol Med 12: 533-540, 2003.
APA
Huang, H., McIntosh, J.L., Fang, L., Szabo, C., & Hoyt, D.G. (2003). Integrin-mediated suppression of endotoxin-induced DNA damage in lung endothelial cells is sensitive to poly(ADP-ribose) polymerase-1 gene deletion. International Journal of Molecular Medicine, 12, 533-540. https://doi.org/10.3892/ijmm.12.4.533
MLA
Huang, H., McIntosh, J. L., Fang, L., Szabo, C., Hoyt, D. G."Integrin-mediated suppression of endotoxin-induced DNA damage in lung endothelial cells is sensitive to poly(ADP-ribose) polymerase-1 gene deletion". International Journal of Molecular Medicine 12.4 (2003): 533-540.
Chicago
Huang, H., McIntosh, J. L., Fang, L., Szabo, C., Hoyt, D. G."Integrin-mediated suppression of endotoxin-induced DNA damage in lung endothelial cells is sensitive to poly(ADP-ribose) polymerase-1 gene deletion". International Journal of Molecular Medicine 12, no. 4 (2003): 533-540. https://doi.org/10.3892/ijmm.12.4.533