Small interfering RNA mediated Poly (ADP-ribose) Polymerase-1 inhibition upregulates the heat shock response in a murine fibroblast cell line
© Aneja et al; licensee BioMed Central Ltd. 2011
Received: 20 January 2010
Accepted: 23 February 2011
Published: 23 February 2011
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).
Poly (ADP-ribose) polymerase-1 (PARP-1) is a highly conserved chromatin bound enzyme [1, 2] and plays an important role in DNA repair, gene transcription, cell-cycle progression, cell death, and maintenance of genomic integrity [3–5]. PARP-1 is activated by DNA breaks and cleaves nicotinamide adenine dinucleotide (NAD+) into nicotinamide resulting in ADP-ribose moieties; these moieties covalently attach to various acceptor proteins including PARP itself. The continued activation of PARP leads to depletion of its substrate NAD+ with consequent depletion of ATP, energy failure and cell death .
In addition to its influence on chromatin structure and stability, recent studies indicate PARP-1 plays a role in gene-specific transcription [7–9]. PARP-1 regulates transcription by modifying chromatin-associated proteins and acts as a cofactor for transcription factors, most notably NF-κB and AP-1 [10, 11]. Genetic deletion of PARP-1 attenuates tissue injury after ischemia and reperfusion, streptozocin-induced diabetes, endotoxic and hemorrhagic shock, heat stroke and localized colonic inflammation [12–19]. The benefits conferred by pharmacological inhibitors of poly (ADP-ribosylation) in diverse experimental disease models further reiterate the importance of PARP-1 as an important pharmacological target [20, 21]
Oxidative injury and ATP depletion also leads to activation of heat shock factor (HSF)-1, a major transcription factor responsible for increased transcription of genes encoding heat shock proteins, particularly heat shock protein-70 [22, 23]. HSP-70 provides cytoprotection from a variety of inflammatory insults, including oxidative stress, viral infections and ischemia-reperfusion injury [24, 25]. Previously in an in vivo model of myocardial ischemia/reperfusion injury, we showed that cardioprotection conferred on PARP-1-/- mice is associated with enhanced HSF-1 activity and increased expression of HSP-70 as compared to wild-type mice .
Similarly, Fossati et al. documented increased HSP-70 expression in murine PARP-1 deficient fibroblasts as compared to wild type fibroblasts . In gene knockout cell lines, unexpected compensatory or redundant mechanisms develop in response to the missing gene and can confound experimental observations. To verify that the upregulation of the heat shock response in PARP-1 deficient mice is not a compensatory response to the missing PARP-1 gene, we employed post-transcriptional gene silencing technology by RNA interference. Specifically, we utilized small interfering RNA (siRNA) to silence PARP-1 gene and hypothesized that the heat shock response is negatively modulated by PARP-1 activation in fibroblasts; therefore siRNA mediated PARP-1 inhibition would lead to augmentation of the heat shock response.
Material and methods
Mouse fibroblasts from wild-type mice were created by immortalization by a standard 3T3 protocol . Unless noted otherwise, all reagents were from Sigma-Aldrich (St. Louis MO). Cell monolayers were grown at 37°C in 5% CO2 air in Dulbecco's modified Eagle medium (DMEM) (Gibco Technologies, Grand Island, NY) containing 10% fetal bovine serum (FBS), penicillin (100 U/ml), and streptomycin (100 μg/ml). At 75-80% confluence, fibroblasts were subjected to heat shock at 43°C for 45 min followed by recovery at 37°C up to 4 h. If needed, cells were pretreated with PARP inhibitor 1, 5 dihydroxyisoquinoline (DIQ, 100 μM; Sigma, St. Louis, MO) for 45 min in all experiments.
Nuclear protein extraction
All nuclear protein extraction procedures were performed on ice with ice-cold reagents. Cells were washed twice with phosphate-buffered saline (PBS) and harvested by scraping. Cells were pelleted in 1 ml of PBS at 14,000 rpm for 1 min. The pellet was washed twice with PBS and resuspended in lysis buffer [10 mM Tris-HCl (pH 7.8), 10 mM KCl, 1 mM ethylene glycol tetra acetic acid (EGTA), 5 mM MgCl2, 1 mM dithiothreitol (DTT), and 0.5 mM phenylmethylsulfonyl fluoride (PMSF)]. The suspension was incubated on ice for 15 min and Nonidet P-40 was added followed by centrifugation at 4°C at 2,000 rpm for 5 min. The supernatant was discarded and the cell pellet was dissolved in extraction buffer (20 mM Tris-HCl, pH 7.8, 32 mM KCl, 0.2 mM EGTA, 5 mM MgCl2, 1 mM DTT, 0.5 mM PMSF and 25% v/v glycerol) was added to the nuclear pellet and incubated on ice for 15 min. Nuclear proteins were isolated by centrifugation at 14,000 rpm at 4°C for 10 min. Protein concentrations of the resultant supernatants were determined using the Bradford assay. Nuclear proteins were stored at -70°C until used for electromobility gel shift assays (EMSA).
EMSA were performed as previously described . An oligonucleotide probe corresponding to an HSF-1 consensus sequence (5'-GCC TCG ATT GTT CGC GAA GTT TCG-3') was labeled with γ-[32P] ATP using T4 polynucleotide kinase (Promega) and purified in Bio-Spin chromatography columns (GE Healthcare, Buckinghamshire, UK). For each sample 4 μg of nuclear proteins were incubated with Bandshift buffer (10 mM Tris, 40 mM KCl, 1 mM (ethylene diamine tetra acetic acid) EDTA, 1 mM DTT, 50 ng/ml poly d(I-C), 10% glycerol) at room temperature with subsequent addition of the radiolabeled oligonucleotide probe for 30 min. Protein-nucleic acid complexes were resolved using a nondenaturing polyacrylamide gel consisting of 5% acrylamide (29:1 ratio of acrylamide: bisacrylamide) and run in 0.25 X Tris/Borate/EDTA (TBE) (45 mM Tris, 45 mM boric acid, 1 mM EDTA) for 1 h at 30 mA constant current. Gels were transferred to Whatman 3 MM paper, dried under a vacuum at 80°C for 1 h, and used to expose to X-ray film at -70°C with an intensifying screen.
Real-time reverse transcriptase-PCR analysis
Fibroblasts were subjected to heat shock at 43°C for 45 min followed by recovery at 37°C for 120 min. Cells were harvested in 1 ml of TRI-Reagent as directed by the manufacturer (Molecular Research Center, Cincinnati, OH). Bromochloropropane was used for the extraction. The final RNA pellet was dissolved in nuclease - free water and quantified using a GeneQuant Pro UV spectrophotometer (GE Healthcare). Extracted RNA (1 μg/reaction) was converted to single-stranded cDNA in a 20 μl reaction using the Reverse Transcriptase System Kit (Promega) as directed by the manufacturer. The mixture was heated to 70°C for 10 min, maintained at 42°C for 30 min, and then heated to 95°C for 5 min using a Gene Amp PCR System 9700 (Applied Biosystems, Foster City, CA). TaqMan Gene Expression Assays for HSP-70 (GENBANK accession no. NM 010479), 18 S RNA (endogenous control) and real-time PCR reagents were purchased from Applied Biosystems (Foster City, CA). Reaction mixtures for PCR were assembled as follows: 10 μl TaqMan Universal PCR Master Mix, 1 μl of each Gene Expression Assay mix, 1 μl cDNA template and 7 μl of water. PCR reactions were performed in an Applied Biosystems thermocycler 7300 Real Time PCR System by incubating at 50°C for 2 min, 95°C for 10 min, 95°C for 15 s, and 60°C for 1 min; the two final conditions were repeated for 40 cycles. Each sample was assayed in duplicate and the values were averaged. A ΔΔ Ct relative quantification method was used to calculate mRNA levels for HSP-70 in the samples. Results were normalized relative to 18 S rRNA expression.
SiRNA-mediated inhibition of PARP expression
Stealth small interference RNA (siRNA) sequences for PARP (sequences) were designed using Invitrogen on line software (Block-iT™RNAi Express) to target PARP-1 mRNA (accession number NM007415). Small interfering RNA (siRNA)-mediated silencing of the PARP-1 gene was performed using 21-bp siRNA duplexes purchased from Ambion (Austin, TX). The coding strand for PARP-1 siRNA was 5'-AUG UCG GCA AAG UAG AUC CCU UUC C-3'. An unrelated siRNA sequence (catalog number 12935-113) was used as a control. In this experiment, cells were incubated for 6 h and transfected at approximately 40% confluency with 20nm siRNA duplexes using Lipofectamine™2000 (Invitrogen, Carlsbad, CA) according to the manufacturer's instructions. All the experiments were performed 18 h after transfection. The efficiency and specificity of siRNA gene knockdown of PARP-1 was determined by real time PCR for PARP-1 mRNA and Western blotting for PARP-1 expression.
Western blot analysis
Western blot analyses were performed as previously described . Briefly, whole cell lysates containing 30 μg of protein were boiled in equal volumes of loading buffer (125 mM Tris, pH 6.8, 4% sodium dodecyl sulfate (SDS), 20% glycerol, and 10% β-mercaptoethanol). Proteins were separated on 8-16% polyacrylamide gels and subsequently transferred to polyvinylidene difluoride (PVDF) membranes (GE Healthcare, Buckinghamshire, UK). For immunoblotting, membranes were blocked with 5% non-fat dried milk in PBS for 1 h. Primary antibodies against the inducible isoform of HSP-70 (Stressgen, Victoria, BC, Canada) were applied at 1:2500 dilution for 1 h. After washing twice with PBS containing 0.5% Tween 20 (PBST), secondary antibody (horse radish peroxidase-conjugated goat anti- rabbit immunoglobulin G, Stressgen, Victoria, British Columbia) was applied at 1:4,000 dilution for 1 h. Blots were washed in PBST thrice for 10 min, incubated in Enhanced Chemiluminescence Reagent (GE Healthcare), and used to expose X-ray film (GE Healthcare).
Nuclear extracts were incubated with normal mouse IgG-AC (20 μl Santa Cruz, sc-2343) and incubated for 30 min at 4°C. Anti-PARP antibody (10 μl Biomol, SA-250) or HSF-1 antibody (Stressgen, SPA-950) and non-specific IgG was added to the supernatant for 1 h at 4°C. Thereafter, protein A/G PLUS-Agarose beads were added (20 μl Santa Cruz Biotechnology, sc2003) and the samples were incubated overnight at 4°C. Beads were washed three times in volume 1xPBS and resuspended in 2 X SDS- polyacrylamide gel electrophoresis (PAGE) sample buffers and analyzed by 8% SDS-PAGE. The proteins were then transferred onto PVDF membranes (GE Healthcare, Buckinghamshire, UK). The membranes were blocked in 1X PBST containing 5% nonfat dry milk and incubated with an HSF-1 antibody (Stressgen, SPA-950) or Anti-PARP antibody (10 μl Biomol, SA-250). The membranes were washed and incubated with a polyclonal rabbit anti -rat antibody conjugated to horseradish peroxidase (Stressgen, SAB-200). Immunoreaction was visualized by chemiluminescence.
All values in the figures and text are expressed as mean ± SEM. The results were examined by analysis of variance followed by the Bonferroni's correction post hoc t test. A p-value less than 0.05 were considered significant.
Inhibition of PARP-1 expression by RNA interference augments HSP-70 protein expression
HSP-70 mRNA expression is increased with inhibition of PARP-1 expression
HSF-1 DNA-binding activity is increased with inhibition of PARP-1
PARP-1 interacts with HSF-1
Because previous studies reported that PARP-1 may regulate transcription factors by a direct physical association [7, 8, 30] we next explored the possibility of a protein-protein interaction between PARP-1 and HSF-1.
To determine if there is protein-protein interaction between PARP-1 and HSF-1, nuclear lysates were immunoprecipitated with antibodies against HSF-1. As shown in Figure 5B, HSF-1 was efficiently immunoprecipitated with HSF-1 antibody and no signal was observed when mouse IgG was used as a control for immunoprecipitation. Immunoblotting of the HSF-1immunoprecipitated proteins with PARP-1 antibody demonstrated the presence of PARP-1 suggesting that HSF-1and PARP-1 physically interact with each other. Wild-type cells treated with DIQ (PARP-1inhibitor) that had not been subjected to heat shock demonstrated a slight increase in nuclear HSF-1 content as compared to control cells. Cells pretreated with DIQ and subsequently exposed to heat shock demonstrated increased HSF-1 binding to PARP-1 as compared to untreated control heat shocked wild-type cells (Figure 5B).
To confirm the results obtained by HSF-1 immunoprecipitation, we conducted the reverse experiment by immunoprecipitating with a PARP-1 antibody and subsequent analysis of the immunoprecipitate for HSF-1. Similar to our results above, cells pretreated with a PARP-1inhibitor demonstrated a slight increase in HSF-1 content as compared to control cells. Analogous to our finding above, nuclear lysates exposed to a PARP-1 inhibitor prior to heat shock demonstrated increased HSF-1 binding to PARP-1 in comparison to cells that were not exposed.
Thus, in this study we demonstrate that PARP-1 physically interacts with HSF-1 in resting and heat shocked cells. Furthermore, these immunoprecipitation studies confirm that exposure to heat shock increases the nuclear HSF-1 binding to PARP-1.
PARP-1 catalyses the covalent attachment of ADP-ribose units on to the γ carboxyl group of glutamate residues in acceptor proteins including PARP-1 itself [5, 31, 32]. Each of these ADP-ribose units has an adenine moiety capable of base stacking and hydrogen bonding, along with two phosphate groups that carry negative charges. These polymers cause profound changes in the structure and function of key proteins that respond to DNA damage. For example, proteins like histones, topoisomerases I and II, and DNA helicases undergo poly (ADP-ribosylation) and help in regulation of chromatin structure and genomic integrity [3–5]. However, a growing body of evidence suggests that in addition to its regulation of chromatin structure, PARP-1 also plays a key role in gene-specific transcription.
PARP-1 regulates gene-specific transcription by two possible mechanisms. Kim et al. demonstrated that PARP-1 binds to specific nucleosomes and leads to formation of compact, transcriptionally repressed chromatin structures . Upon activation, PARP-1 is poly (ADP-ribosylated) and dissociates from chromatin leading to formation of decondensed, transcriptionally active euchromatin structures. It has also been proposed that PARP-1 is part of a nucleosome complex along with a histone variant macroH2A (mH2A). At baseline conditions, mH2A and an inactive PARP-1 are associated with the HSP-70 promoter. Upon heat shock, HSP-70 promoter bound PARP-1 is released to activate HSP-70 transcription . Hence, siRNA mediated knockdown of either PARP-1 or mH2A1 downregulated transcription of HSP-70 gene. This observation was complemented by another study that demonstrated chromosomal "puffing" with increased HSP-70 gene expression in Drosophila salivary glands after heat shock . It was proposed that PARP dissociates chromatin proteins at induced chromosomal loci, thus allowing increased transcription of target heat shock genes. In contrast to our study, treatment with an inhibitor of PARP activity reduced puffing and consequently decreased transcription of heat shock genes following heat shock. Our data are consistent with our previous in vivo study of myocardial ischemia-reperfusion injury, where we demonstrated that mice with genetic ablation of PARP-1 exhibit significant cardioprotection, associated with enhanced upregulation of HSF-1 DNA binding in the heart . The reasons for the different response of dipterans and mammals to PARP-1 inhibition are unknown. It is plausible that factors including signaling mediators have evolved different effector proteins that can affect the heat shock response and its regulation by PARP-1.
Another potential mechanism which may be more relevant to this study entails the role of PARP as a gene specific transcription enhancer/promoter binding cofactor activity that can enhance or inhibit gene expression. PARP-1 has been shown to interact with the transcription factors NF-κB, HTLV Tax-1 and RAR and this was associated with increased expression from dependent promoters [7–9]. Similarly, it has been suggested that PARP-1 is a co-transcription factor for the mammalian achaete-scute homologue (MASH) gene. PARP-1 is present in an inactive state as part of a co-repressor complex. Upon activation, PARP-1 is required for the dismissal of the co-repressor complex, and a second subsequent event leads to activation of the target MASH gene .
Our experiments indicate that PARP-1 modulates the heat shock response by functioning as a repressing factor of HSP-70 gene expression. We provide two lines of evidence in this regard. First, in this study we demonstrated that knockdown of PARP-1 gene increased HSP-70 gene expression as evidenced by increased DNA-binding activity of HSF-1, HSP-70 mRNA and protein expression. Secondly, using co-immunoprecipitation we demonstrated that PARP-1 may also regulate HSF-1 activation through direct interaction with this transcription factor. Protein-protein interaction is recognized as a mechanism for PARP-1 to function as a specific transcriptional co-activator of NF-κB .
Fossati et al. similarly documented increased HSP-70 expression in murine PARP-1 deficient fibroblasts as compared to wild type fibroblasts . In contrast to our findings, this study was unable to detect PARP-1 and HSF-1 interaction by co-immunoprecipitation studies. While the cell type utilized in the two studies was remarkably similar, the duration of heat shock was different. In our study, the cells were subjected to 45 min of heat shock in comparison to 30 min in the study by Fossati et al. . Other differences that could lead to different results may be the antibody type and protocol design for immunoprecipitation studies.
Other studies have also proven that PARP-1 modulates transcription by direct interaction with AP2 , Oct-1, YY-1  and TEF-1 . PARP has been also shown to alter RNA polymerase II dependent transcription  and to effectively prevent and reverse p53 binding to the palindromic p53 consensus sequence . Before HSF-1 is activated there are a series of processes that involve phosphorylation, translocation from the cytosol to the nucleus, formation of a trimer, binding to heat shock elements (HSE), and initiating HSP-70 gene expression [44–46]. It has been postulated that addition of long ADP-ribose tails to transcription factors can disable or dissociate the binding of transcription factors to their DNA recognition sites, also in part by electrostatic repulsion. This modification results in inhibition of transcription. Poly (ADP-ribosylation) of transcription factors prevents their binding to DNA. On the contrary, inhibition of PARP-1 enables the binding of the transcription factors to their specific DNA sites . Thus, it is possible that both physical interaction with PARP-1 and poly (ADP-ribosylation) of HSF-1 reduce the availability of HSF-1 to initiate transcription. The increase in HSF-1 content, albeit inactive with DIQ pretreatment further reinforces the notion that PARP-1 represses HSP-70 gene transcription. Further studies need to be conducted to understand the precise mechanism as to how and where PARP-1 regulates HSF-1 activation.
In conclusion, our results indicate that PARP-1 serves as a repressing factor of the heat shock response by regulating the expression of HSP-70. Both protein-protein interaction and catalytic activity of the PARP protein play a key role in modulation of the heat shock response.
Funding for this study was provided by the National Institutes of Health to Dr. Rajesh Aneja (grant K08GM076344), Dr. Basilia Zingarelli (grant R01 HL-60730), and Dr. Russell Delude (grant GM37631).
- Ame JC, Spenlehauer C, de Murcia G: The PARP superfamily. Bioessays. 2004, 26: 882-93. 10.1002/bies.20085.PubMedView ArticleGoogle Scholar
- Schreiber V, Dantzer F, Ame JC, de Murcia G: Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol. 2006, 7: 517-28. 10.1038/nrm1963.PubMedView ArticleGoogle Scholar
- de Murcia G, Schreiber V, Molinete M, et al: Structure and function of poly(ADP-ribose) polymerase. Mol Cell Biochem. 1994, 138: 15-24. 10.1007/BF00928438.PubMedView ArticleGoogle Scholar
- de Murcia G, Menissier de Murcia J: Poly(ADP-ribose) polymerase: a molecular nick-sensor. Trends Biochem Sci. 1994, 19: 172-6. 10.1016/0968-0004(94)90280-1.PubMedView ArticleGoogle Scholar
- D'Amours D, Desnoyers S, D'Silva I, Poirier GG: Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J. 1999, 342 (Pt 2): 249-68.PubMedPubMed CentralView ArticleGoogle Scholar
- Chiarugi A: Poly(ADP-ribose) polymerase: killer or conspirator? The 'suicide hypothesis' revisited. Trends Pharmacol Sci. 2002, 23: 122-9. 10.1016/S0165-6147(00)01902-7.PubMedView ArticleGoogle Scholar
- Cervellera MN, Sala A: Poly(ADP-ribose) Polymerase Is a B-MYB Coactivator. J Biol Chem. 2000, 275: 10692-6. 10.1074/jbc.275.14.10692.PubMedView ArticleGoogle Scholar
- Anderson MG, Scoggin KE, Simbulan-Rosenthal CM, Steadman JA: Identification of poly(ADP-ribose) polymerase as a transcriptional coactivator of the human T-cell leukemia virus type 1 Tax protein. J Virol. 2000, 74: 2169-77. 10.1128/JVI.74.5.2169-2177.2000.PubMedPubMed CentralView ArticleGoogle Scholar
- Pavri R, Lewis B, Kim TK, et al: PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator. Mol Cell. 2005, 18: 83-96. 10.1016/j.molcel.2005.02.034.PubMedView ArticleGoogle Scholar
- Aguilar-Quesada R, Munoz-Gamez JA, Martin-Oliva D, et al: Modulation of transcription by PARP-1: consequences in carcinogenesis and inflammation. Curr Med Chem. 2007, 14: 1179-87. 10.2174/092986707780597998.PubMedView ArticleGoogle Scholar
- Hassa PO, Covic M, Hasan S, Imhof R, Hottiger MO: The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B coactivator function. J Biol Chem. 2001, 276: 45588-97. 10.1074/jbc.M106528200.PubMedView ArticleGoogle Scholar
- Zingarelli B, Szabo C, Salzman AL: Blockade of Poly(ADP-ribose) synthetase inhibits neutrophil recruitment, oxidant generation, and mucosal injury in murine colitis. Gastroenterology. 1999, 116: 335-45. 10.1016/S0016-5085(99)70130-7.PubMedView ArticleGoogle Scholar
- Zingarelli B, Salzman AL, Szabo C: Genetic disruption of poly (ADP-ribose) synthetase inhibits the expression of P-selectin and intercellular adhesion molecule-1 in myocardial ischemia/reperfusion injury. Circ Res. 1998, 83: 85-94.PubMedView ArticleGoogle Scholar
- Zingarelli B, O'Connor M, Wong H, Salzman AL, Szabo C: Peroxynitrite-mediated DNA strand breakage activates poly-adenosine diphosphate ribosyl synthetase and causes cellular energy depletion in macrophages stimulated with bacterial lipopolysaccharide. J Immunol. 1996, 156: 350-8.PubMedGoogle Scholar
- Eliasson MJ, Sampei K, Mandir AS, et al: Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia. Nat Med. 1997, 3: 1089-95. 10.1038/nm1097-1089.PubMedView ArticleGoogle Scholar
- Liaudet L, Soriano FG, Szabo E, et al: Protection against hemorrhagic shock in mice genetically deficient in poly(ADP-ribose)polymerase. Proc Natl Acad Sci USA. 2000, 97: 10203-8. 10.1073/pnas.170226797.PubMedPubMed CentralView ArticleGoogle Scholar
- Pieper AA, Brat DJ, Krug DK, et al: Poly(ADP-ribose) polymerase-deficient mice are protected from streptozotocin-induced diabetes. Proc Natl Acad Sci USA. 1999, 96: 3059-64. 10.1073/pnas.96.6.3059.PubMedPubMed CentralView ArticleGoogle Scholar
- Virag L, Szabo C: The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol Rev. 2002, 54: 375-429. 10.1124/pr.54.3.375.PubMedView ArticleGoogle Scholar
- Mota RA, Hernandez-Espinosa D, Galbis-Martinez L, et al: Poly(ADP-ribose) polymerase-1 inhibition increases expression of heat shock proteins and attenuates heat stroke-induced liver injury. Critical care medicine. 2008, 36: 526-34. 10.1097/01.CCM.0000299735.43699.E9.PubMedView ArticleGoogle Scholar
- Veres B, Gallyas F, Varbiro G, et al: Decrease of the inflammatory response and induction of the Akt/protein kinase B pathway by poly-(ADP-ribose) polymerase 1 inhibitor in endotoxin-induced septic shock. Biochem Pharmacol. 2003, 65: 1373-82. 10.1016/S0006-2952(03)00077-7.PubMedView ArticleGoogle Scholar
- Jagtap P, Soriano FG, Virag L, et al: Novel phenanthridinone inhibitors of poly (adenosine 5'-diphosphate-ribose) synthetase: potent cytoprotective and antishock agents. Crit Care Med. 2002, 30: 1071-82. 10.1097/00003246-200205000-00019.PubMedView ArticleGoogle Scholar
- Lindquist S, Craig EA: The heat-shock proteins. Annu Rev Genet. 1988, 22: 631-77. 10.1146/annurev.ge.22.120188.003215.PubMedView ArticleGoogle Scholar
- Goldenberg CJ, Luo Y, Fenna M, et al: Purified human factor activates heat shock promoter in a HeLa cell-free transcription system. J Biol Chem. 1988, 263: 19734-9.PubMedGoogle Scholar
- Latchman DS: Heat shock proteins and cardiac protection. Cardiovasc Res. 2001, 51: 637-46. 10.1016/S0008-6363(01)00354-6.PubMedView ArticleGoogle Scholar
- Moseley P: Stress proteins and the immune response. Immunopharmacology. 2000, 48: 299-302. 10.1016/S0162-3109(00)00227-7.PubMedView ArticleGoogle Scholar
- Zingarelli B, Hake PW, O'Connor M, et al: Differential regulation of activator protein-1 and heat shock factor-1 in myocardial ischemia and reperfusion injury: role of poly(ADP-ribose) polymerase-1. Am J Physiol Heart Circ Physiol. 2004, 286: H1408-15. 10.1152/ajpheart.00953.2003.PubMedView ArticleGoogle Scholar
- Fossati S, Formentini L, Wang ZQ, Moroni F, Chiarugi A: Poly(ADP-ribosyl)ation regulates heat shock factor-1 activity and the heat shock response in murine fibroblasts. Biochem Cell Biol. 2006, 84: 703-12. 10.1139/O06-083.PubMedView ArticleGoogle Scholar
- Wang ZQ, Auer B, Stingl L, et al: Mice lacking ADPRT and poly(ADP-ribosyl)ation develop normally but are susceptible to skin disease. Genes Dev. 1995, 9: 509-20. 10.1101/gad.9.5.509.PubMedView ArticleGoogle Scholar
- Chen PC, Wheeler DS, Malhotra V, et al: A green tea-derived polyphenol, epigallocatechin-3-gallate, inhibits IkappaB kinase activation and IL-8 gene expression in respiratory epithelium. Inflammation. 2002, 26: 233-41. 10.1023/A:1019718718977.PubMedView ArticleGoogle Scholar
- Hassa PO, Hottiger MO: The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-kappaB in inflammatory disorders. Cell Mol Life Sci. 2002, 59: 1534-53. 10.1007/s00018-002-8527-2.PubMedView ArticleGoogle Scholar
- Huletsky A, de Murcia G, Muller S, et al: The effect of poly(ADP-ribosyl)ation on native and H1-depleted chromatin. A role of poly(ADP-ribosyl)ation on core nucleosome structure. J Biol Chem. 1989, 264: 8878-86.PubMedGoogle Scholar
- Ogata N, Ueda K, Kawaichi M, Hayaishi O: Poly(ADP-ribose) synthetase, a main acceptor of poly(ADP-ribose) in isolated nuclei. J Biol Chem. 1981, 256: 4135-7.PubMedGoogle Scholar
- Kim MY, Mauro S, Gevry N, Lis JT, Kraus WL: NAD+-dependent modulation of chromatin structure and transcription by nucleosome binding properties of PARP-1. Cell. 2004, 119: 803-14. 10.1016/j.cell.2004.11.002.PubMedView ArticleGoogle Scholar
- Ouararhni K, Hadj-Slimane R, Ait-Si-Ali S, et al: The histone variant mH2A1.1 interferes with transcription by down-regulating PARP-1 enzymatic activity. Genes Dev. 2006, 20: 3324-36. 10.1101/gad.396106.PubMedPubMed CentralView ArticleGoogle Scholar
- Tulin A, Spradling A: Chromatin loosening by poly(ADP)-ribose polymerase (PARP) at Drosophila puff loci. Science. 2003, 299: 560-2. 10.1126/science.1078764.PubMedView ArticleGoogle Scholar
- Ju BG, Solum D, Song EJ, et al: Activating the PARP-1 sensor component of the groucho/TLE1 corepressor complex mediates a CaMKinase IIdelta-dependent neurogenic gene activation pathway. Cell. 2004, 119: 815-29. 10.1016/j.cell.2004.11.017.PubMedView ArticleGoogle Scholar
- Hassa PO, Hottiger MO: A role of poly (ADP-ribose) polymerase in NF-kappaB transcriptional activation. Biol Chem. 1999, 380: 953-9. 10.1515/BC.1999.118.PubMedView ArticleGoogle Scholar
- Kannan P, Yu Y, Wankhade S, Tainsky MA: PolyADP-ribose polymerase is a coactivator for AP-2-mediated transcriptional activation. Nucleic Acids Res. 1999, 27: 866-74. 10.1093/nar/27.3.866.PubMedPubMed CentralView ArticleGoogle Scholar
- Nie J, Sakamoto S, Song D, et al: Interaction of Oct-1 and automodification domain of poly(ADP-ribose) synthetase. FEBS Lett. 1998, 424: 27-32. 10.1016/S0014-5793(98)00131-8.PubMedView ArticleGoogle Scholar
- Oei SL, Griesenbeck J, Schweiger M, et al: Interaction of the transcription factor YY1 with human poly(ADP-ribosyl) transferase. Biochem Biophys Res Commun. 1997, 240: 108-11. 10.1006/bbrc.1997.7621.PubMedView ArticleGoogle Scholar
- Butler AJ, Ordahl CP: Poly(ADP-ribose) polymerase binds with transcription enhancer factor 1 to MCAT1 elements to regulate muscle-specific transcription. Mol Cell Biol. 1999, 19: 296-306.PubMedPubMed CentralView ArticleGoogle Scholar
- Oei SL, Griesenbeck J, Ziegler M, Schweiger M: A novel function of poly(ADP-ribosyl)ation: silencing of RNA polymerase II-dependent transcription. Biochemistry. 1998, 37: 1465-9. 10.1021/bi9727390.PubMedView ArticleGoogle Scholar
- Valenzuela MT, Guerrero R, Nunez MI, et al: PARP-1 modifies the effectiveness of p53-mediated DNA damage response. Oncogene. 2002, 21: 1108-16. 10.1038/sj.onc.1205169.PubMedView ArticleGoogle Scholar
- Mosser DD, Kotzbauer PT, Sarge KD, Morimoto RI: In vitro activation of heat shock transcription factor DNA-binding by calcium and biochemical conditions that affect protein conformation. Proc Natl Acad Sci USA. 1990, 87: 3748-52. 10.1073/pnas.87.10.3748.PubMedPubMed CentralView ArticleGoogle Scholar
- Sorger PK: Heat shock factor and the heat shock response. Cell. 1991, 65: 363-6. 10.1016/0092-8674(91)90452-5.PubMedView ArticleGoogle Scholar
- Van Why SK, Mann AS, Thulin G, et al: Activation of heat-shock transcription factor by graded reductions in renal ATP, in vivo, in the rat. J Clin Invest. 1994, 94: 1518-23. 10.1172/JCI117492.PubMedPubMed CentralView ArticleGoogle Scholar
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