Advances in Biochemistry
Volume 8, Issue 2, June 2020, Pages: 26-37
Received: Mar. 26, 2020;
Accepted: Apr. 13, 2020;
Published: May 14, 2020
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Edna Blotnick-Rubin, Department of Medical Neurobiology, Institute for Medical Research Israel–Canada, Hebrew University of Jerusalem, Jerusalem, Israel
Andras Muhlrad, Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel
Histones are located in the cell nucleus. They are positively charged small proteins which became extracellular upon apoptosis, necrosis, and infection – induced cell death. The mixture of extracellular Histones was shown to bundle Actin filaments and digested by bacterial proteases, which was inhibited by DNA and Actin. Here we studied the interaction of five major family of Histones, H2A, H2B, H3.1, H1 and H4, with DNA and Actin filaments. We found that all the Histones studied bound to DNA, increased the viscosity of Actin containing solutions and bundled Actin filaments in various degrees. The bundling of Actin filaments by Histones was inhibited by DNA, NaCl and DNase1. DNA and Actin filaments also inhibited the proteolysis of the five Histones by Subtilisin, Fusolisin and Pseudomonas Aeruginosa bacterial proteases. Both the degree of the proteolysis and its inhibition was different with various Histones. The results indicate that all the Histones studied bind strongly to the negatively charged DNA and to the Actin filaments.
Interaction of Extracellular Histones with DNA and Actin Filaments, Advances in Biochemistry.
Vol. 8, No. 2,
2020, pp. 26-37.
Tagai C, Morita S, Shiraishi T, Miyaji K, Iwamuro S. Antimicrobial properties of arginine- and lysine-rich histones and involvement of bacterial outer membrane protease T in their diﬀerential mode of actions. Peptides. 2011; 32: 2003–2009.
Wu D, Ingram A, Lahti JH, Mazz B, Grenet J, Kapoor A, et al. Apoptotic release of histones from nucleosomes. J Biol Chem. 2002; 277: 12001–12008.
Wickman GR, Julian L, Mardilovich K, Schumacher S, Munro J, Rath N, et al. Blebs produced by actin-myosin contraction during apoptosis release damage-associated molecular pattern proteins before secondary necrosis occurs. Cell Death Diﬀer. 2013; 20: 1293–1305.
Chen Kang R, Fan XG, Tang D. Release and activity of histone in diseases. Cell Death Dis. 20114; 5: e1370. doi: 10.1038/cddis.2014.337
Allam R, Kumar SV, Darisipudi MN, Anders HJ. Extracellular histones in tissue injury and inﬂammation. J Mol Med. (Berl.) 2014; 92: 465–472.
Sathyan N, Philip R, Chaithanya ER, Anil Kumar PR, Sanjeevan VN, Sing, ISB. (Characterization of histone H2A derived antimicrobial peptides, Harriottins, from Sickleﬁn Chimaera Neoharriotta pinnata (Schnakenbeck, 1931) and Its evolutionary divergence with respect to CO1 and histone H2A. ISRN. Mol Biol. 2013; 1–10.
Robinette D, Wada S, Arroll T, Levy MG, Miller WL, Noga EJ. Antimicrobial activity in the skin of the channel catﬁsh Ictalurus punctatus: characterization of broad-spectrum histone-like antimicrobial proteins. Cell Mol Life Sci. 1998; 54: 467–475.
Lee HS, Park CB, Kim JM, Jang SA, Park IY, Kim MS, et al. (2008). Mechanism of anticancer activity of buforin IIb, a histone H2A-derived peptide. Cancer Lett. 2008; 271: 47–55.
Richards RC, O’Neil DB, Thibault P, Ewart KV. Histone H1: an antimicrobial protein of Atlantic salmon (Salmo salar). Biochem Biophys Res Commun. 2001; 284: 549–555.
Katchalski E, Bichovski-Slomnitzki L, Volcani BE. Action of some water-soluble poly-a-amino-acids on bacteria. Nature 1952; 169: 1095–1096.
Hirsch JG. Bactericidal action of histone. J Exp Med. 1958; 108: 925-44.
Sol A., Skvirsky Y, Blotnick E, Bachrach G, and Muhlrad A. Actin and DNA protect histones from degradation by bacterial proteases but inhibit their antimicrobial activity. Front. Microbiol. 2016; 7: 1248.
Ginsburg I, Mitra RS, Gibbs DF, Varani J, Kohen R. Killing of endothelial cells and release of arachidonic acid. Synergistic effects among hydrogen peroxide, membrane-damaging agents, cationic substances, and proteinases and their modulation by inhibitors. Inflammation. 1993; 17: 295–319.
Blotnick E, Sol A, Muhlrad A. Histones bundle F-actin filaments and affect actin structure. Plos One. 2017; 12 (8): e0183760.
Vasconcellos CA, Allen PG, Wahl ME, Draven JM, Janmey PA, Stossel TP. Reduction in viscosity of cystic fibrosis sputum in vitro by gelsolin. Science. 1994; 263: 969–7121.
Spudich JA, and Watt S. The regulation of rabbit skeletal muscle contraction. Biochemical studies of the interaction of the tropomyosin-troponin complex with actin and the proteolytic fragments of myosin. J Biol Chem. 1971; 246: 4866–71.
Doron L, Coppenhagen-Glazer S, Ibrahim Y, Eini A, Naor R, Rosen G, Bachrach G. Identification and Characterization of Fusolisin, the Fusobacterium nucleatum Autotransporter Serine Protease. Plos One. 2014; 9 (10): e111329.
Uyterhoeven ET, Butler CH, Ko D, Elmore DE. Investigating the nucleic acid interactions and antimicrobial mechanism of buforin II. FEBS Lett. 2008; 582: 1715–18.
Tse WC, Boger DL. A fluorescent intercalator displacement assay for establishing DNA binding selectivity and affinity. Acc Chem Res. 2004; 37: 61–9.
Tang JX, Janmey PA. The polyelectrolyte nature of F-actin and the mechanism of actin bundle formation. J Biol Chem. 1996; 271: 8556–63.
Muhlrad A, Grintsevich EE, Reisler E. Polycation induced actin bundles. Biophys Chem. 2011; 155: 45– 51.
Tang JX, Ito T, Tao T, Traub P, Janmey PA. Opposite effects of electrostatics and steric exclusion on bundle formation by F-actin and other filamentous polyelectrolytes. Biochemistry. 1997; 36: 12600–7.
Blotnick E, Sol A, Bachrach G, Muhlrad, A. Interactions of histatin-3 and histatin-5 with actin. BMC Biochemistry. 2017; 18: 3.
Beyth N, Blotnick-Rubin E, Houri-Haddad Y, Beyth S, Muhlrad. Buforin III Analogs Bind to DNA and Actin and Inhibit Bacterial Growth. Advances in Biochemistry. 2018; 6 (5): 39-46.
Kabsch W, Mannherz HG, Suck D, Pai EF, Holmes KC. Atomic structure of the actin: DNase I complex. Nature. 1990; 347: 37–44.
Mannherz HG, Leigh JB, Leberman R and Pfrang HA. Specific 1: 1 G-actin: DNase 1 complex formed by the action of DNase 1 on F-actin. FEBS Lett. 1975; 60: 34–8.
Sol A, Blotnick E, Bachrach G, Muhlrad A. LL-37 induces polymerization and bundling of actin and affects actin structure. Plos One. 2012; 7: e50078 (2012).
Sol A, Skvirsky Y, Nashef R, Zelentsova K, Burstyn-Cohen T, Blotnick E., Muhlrad A, Bachrach G. Actin enables the antimicrobial action of LL-37 in the presence of microbial protease. J Biol Chem. 2014; 289: 22926-22941.
Welsh MJ, Smith AE (1995) Cystic fibrosis. Sci Am. 1995; 273: 52–59.
Bucki R, Byfield FJ, Janmey PA. Release of the antimicrobial peptide LL-37 from DNA/F-actin bundles in cystic fibrosis sputum. Eur Respir J. 2007; 29: 624–32.
Brogan TD, Ryley HC, Neale L, Yassa J. Soluble proteins of bronchopulmonary secretions from patients with cystic fibrosis, asthma, and bronchitis. Thorax. 1975; 30: 72–79.
Jay X, Tang JX, Wen Q, Bennett A, Kim B, Sheils CA et al. Anionic poly (amino acid) s dissolve F-actin and DNA bundles, enhance DNase activity, and reduce the viscosity of cystic fibrosis sputum. Am J Physiol—Lung Cellular and Molecular Physiol. 2005; 289: L599–L605.
Xu Z, Huang Y, Mao P, Zhang J, Li Y. Sepsis and ARDS: The Dark Side of Histones. Mediators Inflamm. 2015; 2015: 205054.
Xu J, Zhang X, Pelayo R, Monestier M, Ammollo CT, Semeraro F et al. Extracellular histones are major mediators of death in sepsis. Nat Med. 2009; 15: 1318–21.