Small interfering RNA mediated poly (ADP-ribose) polymerase-1 inhibition upregulates the heat shock response in a murine fibroblast cell line

Poly (adp-ribose) polymerase-1 (parp-1) is a highly conserved multifunctional enzyme,and its catalytic activity is stimulated by dna breaks. the activation of parp-1 and subsequent depletion of nicotinamide adenine dinucleotide (nad+) and adenosine triphosphate (atp) contributes to significant cytotoxicity in inflammation of various etiologies. on the contrary,induction of heat shock response and production of heat shock protein 70 (hsp-70) is a cytoprotective defense mechanism in inflammation. recent data suggests that parp-1 modulates the expression of a number of cellular proteins at the transcriptional level. in this study,small interfering rna (sirna) mediated parp-1 knockdown in murine wild-type fibroblasts augmented heat shock response as compared to untreated cells (as evaluated by quantitative analysis of hsp-70 mrna and hsp-70 protein expression). these events were associated with increased dna binding of the heat shock factor-1 (hsf-1),the major transcription factor of the heat shock response. co-immunoprecipitation experiments in nuclear extracts of the wild type cells demonstrated that parp-1directly interacted with hsf-1. these data demonstrate that,in wild type fibroblasts,parp-1 plays a pivotal role in modulating the heat shock response both through direct interaction with hsf-1 and poly (adp-ribosylation). © 2011 aneja et al; licensee biomed central ltd.