These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Lipopolysaccharide activates ERK-PARP-1-RelA pathway and promotes nuclear factor-κB transcription in murine macrophages.
    Author: Liu L, Ke Y, Jiang X, He F, Pan L, Xu L, Zeng X, Ba X.
    Journal: Hum Immunol; 2012 May; 73(5):439-47. PubMed ID: 22391342.
    Abstract:
    Poly(ADP-ribosyl)ation, like acetylation, methylation and phosphorylation, is one of the essential post-translational protein modifications. Poly(ADP-ribose) polymerase 1 (PARP-1), the best characterized member of the PARP family, catalyzes PAR formation, and has been implemented in the in vivo and in vitro inflammatory disease models. However, the exact signaling pathways leading to PARP-1 activation and the molecular mechanisms of activated PARP-1 signaling of inflammatory genes' expression remains to be further elucidated. In the present study, murine macrophages, in vitro stimulated with lipopolysaccharide (LPS), showed a profound activation of PARP-1, and PARP-1-dependent expression of mRNA for interleukin (IL)-1β and IL-18 inflammatory cytokines. Immunoprecipitation assays showed that LPS stimulation enhanced the binding of PARP-1 with p65 (RelA) and poly(ADP-ribosyl)ation of p65, which might account for the upregulated transcription activity of nuclear factor (NF)-κB and the increased expression of proinflammatory genes. The application of various signal pathway inhibitors revealed that besides the canonical ROS-DNA damage signal, ERK pathway modulated the activation of PARP-1. ERK inhibitor blocked the interaction of PARP-1 with ERK1/2, phosphorylation of PARP-1, and poly(ADP-ribosyl)ation of p65, suggesting that ERK-dependent phosphorylation of PARP-1 regulates PARP-1 activity and NF-κB activation. Taken together, our results suggest that an ERK-PARP-1-RelA pathway in macrophages promote inflammatory progression in septic diseases.
    [Abstract] [Full Text] [Related] [New Search]