The Study Of The Mechanism Of PARP-1 Activity Involved In The Transcriptional Regulation Of NF-κB

Poly(ADP-ribose) polymerase (PARP)-1 is an enzyme which is particularly abundant in cell nucleus. In response to DNA-strand breaks,it catalyze the transfer of ADP-ribose units from NAD+ to substrate proteins. PARP-1 plays a key role in the maintenance of genomic integrity,control of cell cycles by physiological stimulation. Recent studies revealed that gene transcription regulated by PARP-1 involved in many cellular processes. The microbial infection triggers the producing of ROS,thereby,impairs DNA. The TLR family senses the molecular signatures of microbial pathogens,and plays a fundamental role in innate immune responses. Many pro-inflammatory gene transcription regulations are associated with activation of NF-κB in immune responses. However,the mechanism of PARP-1 activation and how PARP-1 regulates gene transcription in inflammation disorders are unclear. Our work aims to identify whether PARP-1 can be activated in Ana-1 macrophages by the stimulation of LPS,the ligand of TLR4. How LPS induced the activation of PARP-1 to participate the regulation of gene transcription? Whether PARP-1 and NF-κB are coactivtors in transcriptional regulation?The results will help us to further understand the mechanism of transcriptional regulation induced by PARP-1,and discover other cellular signaling pathways in inflammation processes.