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

Aneja, RK and Sjodin, H and Gefter, JV and Zingarelli, B and Delude, RL (2011) Small interfering RNA mediated poly (ADP-ribose) polymerase-1 inhibition upregulates the heat shock response in a murine fibroblast cell line. Journal of Inflammation, 8.

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Abstract

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. +


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Aneja, RKrka7@pitt.eduRKA70000-0002-7697-275X
Sjodin, H
Gefter, JV
Zingarelli, B
Delude, RL
Date: 25 February 2011
Date Type: Publication
Journal or Publication Title: Journal of Inflammation
Volume: 8
DOI or Unique Handle: 10.1186/1476-9255-8-3
Schools and Programs: School of Medicine > Critical Care Medicine
School of Medicine > Pathology
School of Medicine > Pediatrics
Refereed: Yes
Date Deposited: 17 Nov 2016 21:01
Last Modified: 03 Apr 2021 23:55
URI: http://d-scholarship.pitt.edu/id/eprint/30179

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