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Protein & Peptide Letters


ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Review Article

Methods of PARP-1 Determination and its Importance in Living Organisms

Author(s): Zuzanna Zielińska, Łukasz Ołdak* and Ewa Gorodkiewicz

Volume 29, Issue 6, 2022

Published on: 27 May, 2022

Page: [496 - 504] Pages: 9

DOI: 10.2174/0929866529666220405160715

Price: $65


PARP-1 is one of the 18 PARP enzymes that are involved in important processes at the cellular level. The most important tasks of PARP-1 are to detect and repair DNA damage and to prevent processes of apoptosis. By finding and using new strategies for marking and detecting the activity of this protein, it is possible to identify more and more tasks in which it participates. In pathological states, PARP-1 activity increases significantly. Since the 1980s, scientists have been searching for and discussing substances that may inhibit PARP-1 activity and disrupt DNA damage response pathways. In this way, unwanted cells could be destroyed. The paper presents a short description of the methods used in the determination of PARP-1 by various research groups. A critical approach to each of them was also made by pointing to the advantages and disadvantages of the described analytical methods. The literature review contains information on methods useful for PARP-1 determination, such as SPR, QCM, CL and FL, DPV, SDS-PAGE with MS, MALDI MS, Western Blot, ELISA and ATR-FTIR spectroscopy. It also includes analysis of the results of research on inhibitors that may be effective in the diagnosis and treatment of cancer and other diseases.

Keywords: PARP-1, PARP-1 functions, cancer, PARP-1 determination, living organisms, ELISA.

Graphical Abstract
Dal Piaz, F.; Ferro, P.; Vassallo, A.; Vasaturo, M.; Forte, G.; Chini, M.G.; Bifulco, G.; Tosco, A.; De Tommasi, N. Identification and mechanism of action analysis of the new PARP-1 inhibitor 2″-hydroxygenkwanol A. Biochim. Biophys. Acta, 2015, 1850(9), 1806-1814.
[] [PMID: 25999161]
Bai, P. Biology of poly(ADP-Ribose) polymerases: The factotums of cell maintenance. Mol. Cell, 2015, 58(6), 947-958.
[] [PMID: 26091343]
Wiśnik, E.; Ryksa, M.; Koter-Michalak, M. PARP1 inhibitors: Contemporary attempts at their use in anticancer therapy and future perspective. Postepy Hig. Med. Dosw., 2016, 70, 280-294.
[] [PMID: 27117104]
Dębska, S.; Kubicka, J.; Czyżykowski, R.; Habib, M.; Potemski, P. PARP inhibitors-theoretical basis and clinical application. Postepy Hig. Med. Dosw., 2012, 66, 311-321.
[] [PMID: 22706117]
Loeffler, P.A.; Cuneo, M.J.; Mueller, G.A.; DeRose, E.F.; Gabel, S.A.; London, R.E. Structural studies of the PARP-1 BRCT domain. BMC Struct. Biol., 2011, 11(1), 37.
[] [PMID: 21967661]
Langelier, M-F.; Planck, J.L.; Roy, S.; Pascal, J.M. Crystal structures of poly(ADP-ribose) polymerase-1 (PARP-1) zinc fingers bound to DNA: Structural and functional insights into DNA-dependent PARP-1 activity. J. Biol. Chem., 2011, 286(12), 10690-10701.
[] [PMID: 21233213]
Papeo, G.; Avanzi, N.; Bettoni, S.; Leone, A.; Paolucci, M.; Perego, R.; Quartieri, F.; Riccardi-Sirtori, F.; Thieffine, S.; Montagnoli, A.; Lupi, R. Insights into PARP inhibitors selectivity using fluorescence polarization and surface plasmon resonance binding assays. J. Biomol. Screen., 2014, 19(8), 1212-1219.
[] [PMID: 24916412]
Bai, P.; Cantó, C. The role of PARP-1 and PARP-2 enzymes in metabolic regulation and disease. Cell Metab., 2012, 16(3), 290-295.
[] [PMID: 22921416]
Corda, D.; Di Girolamo, M. Functional aspects of protein mono-ADP-ribosylation. EMBO J., 2003, 22(9), 1953-1958.
[] [PMID: 12727863]
Kiliańska, Z.M.; Zołnierczyk, J.; Węsierska-Gądek, J. Biological activity of poly(ADP-ribose)polymerase-1. Postepy Hig. Med. Dosw., 2010, 64, 344-363.
[PMID: 20679690]
Kluzek, K.; Białkowska, A.; Koczorowska, A.; Zdzienicka, M.Z. Poly(ADP-ribose) polymerase (PARP) inhibitors in BRCA1/2 cancer therapy. Postepy Hig. Med. Dosw., 2012, 66, 372-384.
[] [PMID: 22706123]
Musacchio, L.; Caruso, G.; Pisano, C.; Cecere, S.C.; Di Napoli, M.; Attademo, L.; Tambaro, R.; Russo, D.; Califano, D.; Palaia, I.; Muzii, L.; Benedetti Panici, P.; Pignata, S. PARP inhibitors in endometrial cancer: Current status and perspectives cancer management and research. Cancer Manag. Res., 2020, 12, 6123-6135.
[] [PMID: 32801862]
Lord, C.J.; Ashworth, A. Targeted therapy for cancer using PARP inhibitors. Curr. Opin. Pharmacol., 2008, 8(4), 363-369.
[] [PMID: 18644251]
Virág, L.; Robaszkiewicz, A.; Rodriguez-Vargas, J.M.; Oliver, F.J. Poly(ADP-ribose) signaling in cell death. Mol. Aspects Med., 2013, 34(6), 1153-1167.
[] [PMID: 23416893]
Bai, P.; Cantó, C.; Oudart, H.; Brunyánszki, A.; Cen, Y.; Thomas, C.; Yamamoto, H.; Huber, A.; Kiss, B.; Houtkooper, R.H.; Schoonjans, K.; Schreiber, V.; Sauve, A.A.; Menissier-de Murcia, J.; Auwerx, J. PARP-1 inhibition increases mitochondrial metabolism through SIRT1 activation. Cell Metab., 2011, 13(4), 461-468.
[] [PMID: 21459330]
Mangerich, A.; Bürkle, A. Pleiotropic cellular functions of PARP1 in longevity and aging: Genome maintenance meets inflammation. Oxid. Med. Cell. Longev., 2012, 2012321653
[] [PMID: 23050038]
Masutani, M.; Nakagama, H.; Sugimura, T. Poly(ADP-ribosyl)ation in relation to cancer and autoimmune disease. Cell. Mol. Life Sci., 2005, 62(7-8), 769-783.
[] [PMID: 15868402]
Durkacz, B.W.; Irwin, J.; Shall, S. Inhibition of (ADP-ribose)n biosynthesis retards DNA repair but does not inhibit DNA repair synthesis. Biochem. Biophys. Res. Commun., 1981, 101(4), 1433-1441.
[] [PMID: 6272786]
Rankin, P.W.; Jacobson, E.L.; Benjamin, R.C.; Moss, J.; Jacobson, M.K. Quantitative studies of inhibitors of ADP-ribosylation in vitro and in vivo. J. Biol. Chem., 1989, 264(8), 4312-4317.
[] [PMID: 2538435]
Curtin, N.J. PARP inhibitors for cancer therapy. Expert Rev. Mol. Med., 2005, 7(4), 1-20.
[] [PMID: 15836799]
Ferraris, D.V. From Concept to Clinic. Evolution of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. From concept to clinic. J. Med. Chem., 2010, 53(12), 4561-4584.
[] [PMID: 20364863]
Beneke, S.; Diefenbach, J.; Bürkle, A. Poly(ADP-ribosyl)ation inhibitors: Promising drug candidates for a wide variety of pathophysiologic conditions. Int. J. Cancer, 2004, 111(6), 813-818.
[] [PMID: 15300792]
Peralta-Leal, A.; Rodríguez, M.I.; Oliver, F.J. Poly(ADP-ribose)polymerase-1 (PARP-1) in carcinogenesis: Potential role of PARP inhibitors in cancer treatment. Clin. Transl. Oncol., 2008, 10(6), 318-323.
[] [PMID: 18558578]
Southan, G.J.; Szabó, C. Poly(ADP-ribose) polymerase inhibitors. Curr. Med. Chem., 2003, 10(4), 321-340.
[] [PMID: 12570705]
Lunec, J.; George, A.M.; Hedges, M.; Cramp, W.A.; Whish, W.J.; Hunt, B. Post-irradiation sensitization with the ADP-ribosyltransferase inhibitor 3-acetamidobenzamide. Br. J. Cancer Suppl., 1984, 6, 19-25.
[PMID: 6320851]
Homola, J. Surface plasmon resonance sensors for detection of chemical and biological species. Chem. Rev., 2008, 108(2), 462-493.
[] [PMID: 18229953]
Gorodkiewicz, E.; Regulska, E.; Wojtulewski, K. Development of an SPR imaging biosensor for determination of cathepsin G in saliva and white blood cells. Mikrochim. Acta, 2011, 173(3-4), 407-413.
[] [PMID: 21660086]
Gorodkiewicz, E.; Sieńczyk, M.; Regulska, E.; Grzywa, R.; Pietrusewicz, E.; Lesner, A.; Łukaszewski, Z. Surface plasmon resonance imaging biosensor for cathepsin G based on a potent inhibitor: Development and applications. Anal. Biochem., 2012, 423(2), 218-223.
[] [PMID: 22369897]
Smith, E.A.; Corn, R.M. Surface plasmon resonance imaging as a tool to monitor biomolecular interactions in an array based format. Appl. Spectrosc., 2003, 57(11), 320A-332A.
[] [PMID: 14658142]
Sankiewicz, A.; Puzan, B.; Gorodkiewicz, E. Biosesnors SPRI as a diagnostic tool in the future. Chemik, 2014, 68(6), 528-535.
Kostur, A.; Ostrowska, H.; Kulczynska, H.; Galar, M.; Kłoczko, J. Plasma proteasome 20S activity in patients with newly diagnosed multiple myeloma. Acta Haematol. Pol., 2012, 43(2a), 155-159.
William, H. King, Jr. Piezoelectric sorption detector. Anal. Chem., 1964, 36(9), 1735-1739.
Föll, H. Piezo electricity and related effects.Available from:, (Accessed on: November 21, 2021).
Deakin, M.R.; Buttry, D.A. Elektrochemical applications of the quartz crystal microbalance. Anal. Chem., 1989, 61(20), 1147A-1154A.
Gabrielli, C.; Keddam, M.; Torresi, R. Calibration of the electrochemical quartz crystal microbalance. J. Electrochem. Soc., 1991, 138(9), 2657-2660.
Czanderna, A.W.; Lu, C. Introduction, history, and overview of applications of piezoelectric quartz crystal microbalances. Methods Phenom., 1984, 7, 1-18.
Yang, H.; Li, P.; Wang, D.; Liu, Y.; Wei, W.; Zhang, Y.; Liu, S. Quartz crystal microbalance detection of Poly(ADP-ribose) polymerase‐1 based on gold nanorods signal amplification. Anal. Chem., 2019, 91(17), 11038-11044.
[] [PMID: 31257855]
Lu, C.; Song, G.; Lin, J.M. Reactive oxygen species and their chemiluminescence-detection methods. Trac-Trend. Trends Analyt. Chem., 2006, 25(10), 985-995.
Huang, X.; Ren, J. Chemiluminescence detection for capillary electrophoresis and microchip capillary electrophoresis. Trac-Trend. Trends Analyt. Chem., 2006, 25(2), 155-166.
Li, L.N.; Li, N.B.; Luo, H.Q. A new chemiluminescence method for the determination of nickel ion. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2006, 64(2), 391-396.
[] [PMID: 16563853]
Xu, E.; Yang, H.; Li, P.; Wang, Z.; Liu, Y.; Wei, W.; Liu, S. Dual-mode detection of PARP-1 fluorescence and chemiluminescence. Sensor. Acutat. Sens. Actuators B Chem., 2020, 330, 1-7.
Valeur, B.; Berberan-Santos, M.N. Molecular fluorescence: Principles and applications; Wiley-VCH, 2012, pp. 1-569.
Valeur, B.; Berberan-Santos, M.N. A brief history of fluorescence and phosphorescence before the emergence of quantum theory. J. Chem. Educ., 2011, 88(6), 731-738.
He, D.; Chen, B.; Tian, Q.; Yao, S. Simultaneous determination of five anthraquinones in medicinal plants and pharmaceutical preparations by HPLC with fluorescence detection. J. Pharmaceut. Biomed, 2009, 49(4), 1123-1127.
[] [PMID: 19297114]
Li, D.; Li, C.; Liang, A.; Jiang, Z. SERS and fluorescence dual-mode sensing trace hemin and K+ based on G-quarplex/hemin DNAzyme catalytic amplification. Sensor. Acutat. Sens. Actuators B Chem., 2019, 297126799
Hou, Y.; Guo, X.; Liu, W.; Zhang, L.; Lv, C.; Jin, Y.; Zhang, Z. Paper-based immunosensor with NH2-MIL-53(Fe) as stable and multifunctional signal label for dual-mode detection of prostate specific antigen. J. Lumin., 2021, 117708117708
Soldani, C.; Bottone, M.G.; Pellicciari, C.; Scovassi, A.I. Two-color fluorescence detection of Poly (ADP-Ribose) Polymerase-1 (PARP-1) cleavage and DNA strand breaks in etoposide-induced apoptotic cells. Eur. J. Histochem., 2001, 45(4), 389-392.
[] [PMID: 11846007]
Zhou, X.; Wang, C.; Wang, Z.; Yang, H.; Wei, W.; Liu, Y.; Liu, S. Renewable electrochemical sensor for PARP-1 activity detection based on host-guest recognition. Biosens. Bioelectron., 2020, 148111810
[] [PMID: 31710960]
Hoyos-Arbeláez, J.; Vázquez, M.; Contreras-Calderón, J. Electrochemical methods as a tool for determining the antioxidant capacity of food and beverages: A review. Food Chem., 2017, 221, 1371-1381.
[] [PMID: 27979102]
Simões, F.R.; Xavier, M.G. Electrochemical sensors, in micro and nano technologies, nanoscience and its applications; William Andrew Publishing: Norwich, NY, 2017, pp. 155-178.
Gupta, V.K.; Jain, R.; Radhapyari, K.; Jadon, N.; Agarwal, S. Voltammetric techniques for the assay of pharmaceuticals--a review. Anal. Biochem., 2011, 408(2), 179-196.
[] [PMID: 20869940]
Liu, Y.; Fan, J.; Shangguan, L.; Liu, Y.; Wei, Y.; Wei, W.; Liu, S. Ultrasensitive electrochemical detection of poly (ADP-ribose) polymerase-1 via polyaniline deposition. Talanta, 2018, 180, 127-132.
[] [PMID: 29332790]
Jha, R.; Agarwal, A.; Mahfouz, R.; Paasch, U.; Grunewald, S.; Sabanegh, E.; Yadav, S.P.; Sharma, R. Determination of Poly (ADP-ribose) polymerase (PARP) homologues in human ejaculated sperm and its correlation with sperm maturation. Fertil. Steril., 2009, 91(3), 782-790.
[] [PMID: 18339380]
Liang, X.; Bai, J.; Liu, Y.H.; Lubman, D.M. Characterization of SDS-PAGE-separated proteins by matrix-assisted laser desorption/ionization mass spectrometry. Anal. Chem., 1996, 68(6), 1012-1018.
[] [PMID: 8651486]
Righetti, P.G.; Candiano, G. Recent advances in electrophoretic techniques for the characterization of protein biomolecules: A poker of aces. J. Chromatogr. A, 2011, 1218(49), 8727-8737.
[] [PMID: 21536293]
Montaudo, G.; Samperi, F.; Montaudo, M.S. Characterization of synthetic polymers by MALDI-MS. Prog. Polym. Sci., 2006, 31(3), 277-357.
Gilabert, M.; Launay, S.; Ginestier, C.; Bertucci, F.; Audebert, S.; Pophillat, M.; Toiron, Y.; Baudelet, E.; Finetti, P.; Noguchi, T.; Sobol, H.; Birnbaum, D.; Borg, J.P.; Charafe-Jauffret, E.; Gonçalves, A. Poly(ADP-ribose) polymerase 1 (PARP1) overexpression in human breast cancer stem cells and resistance to olaparib. PLoS One, 2014, 9(8)e104302
[] [PMID: 25144364]
Morris, J.H.; Knudsen, G.M.; Verschueren, E.; Johnson, J.R.; Cimermancic, P.; Greninger, A.L.; Pico, A.R. Affinity purification-mass spectrometry and network analysis to understand protein-protein interactions. Nat. Protoc., 2014, 9(11), 2539-2554.
[] [PMID: 25275790]
Isabelle, M.; Moreel, X.; Gagné, J.P.; Rouleau, M.; Ethier, C.; Gagné, P.; Hendzel, M.J.; Poirier, G.G. Investigation of PARP-1, PARP-2, and PARG interactomes by affinity-purification mass spectrometry. Proteome Sci., 2010, 8(22), 22.
[] [PMID: 20388209]
Stanta, G. Protein immunodetection in Guidelines for molecular analysis in archive tissues; Springer, 2011, pp. 271-285.
Shah, G.M.; Kandan-Kulangara, F.; Montoni, A.; Shah, R.G.; Brind’amour, J.; Vodenicharov, M.D.; Affar, B. Approaches to detect PARP-1 activation in vivo, in situ, and in vitro. Methods Mol. Biol., 2011, 780, 3-34.
[] [PMID: 21870251]
Blancher, C.; Jones, A. SDS-PAGE and western blotting techniques. Methods Mol. Med., 2001, 57, 145-162.
[] [PMID: 21340897]
Clark, M.F.; Lister, R.M.; Bar-Joseph, M. ELISA techniques. Methods Enzymol., 1986, 118, 742-766.
Crowther, J.R. ELISA. Theory and practice. Methods Mol. Biol., 1995, 42, 1-218.
[] [PMID: 7655571]
Voller, A.; Bidwell, D.E.; Bartlett, A. The enzyme-linked immunosorbent assay (ELISA); Guernsey Dynatech Europe: UK, 1979.
Kępska, M.; Futoma-Kołoch, B. Immunoenzymatic ELISA test – an operating principle and reaction optimization; Laboratorium Medyczne, 2018, pp. 42-49.
Moonen, H.J.J.; Geraets, L.; Vaarhorst, A.; Bast, A.; Wouters, E.F.M.; Hageman, G.J. Theophylline prevents NAD+ depletion via PARP-1 inhibition in human pulmonary epithelial cells. Biochem. Biophys. Res. Commun., 2005, 338(4), 1805-1810.
[] [PMID: 16289039]
Glassford, S.E.; Byrne, B.; Kazarian, S.G. Recent applications of ATR FTIR spectroscopy and imaging to proteins. Biochim. Biophys. Acta, 2013, 1834(12), 2849-2858.
[] [PMID: 23928299]
Krüger, A.; Bürkle, A.; Hauser, K.; Mangerich, A. Real-time monitoring of PARP1-dependent PARylation by ATR-FTIR spectroscopy. Nat. Commun., 2020, 11(1), 2174.
[] [PMID: 32358582]

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