Joanna GOLA, Aleksandra SKUBIS, Bartosz SIKORA, Celina KRUSZNIEWSKA-RAJS, Jolanta ADAMSKA, Urszula MAZUREK, Barbara STRZALKA-MROZIK, Grzegorz CZERNEL, Mariusz GAGOS

Expression profiles of genes related to melatonin and oxidative stress in human renal proximal tubule cells treated with antibiotic amphotericin B and its modified forms

Melatonin protects cells from oxidative stress caused by antibiotics. Through the generation of reactive oxygen species (ROS), amphotericin B (AmB) causes oxidative injuries of the kidneys and liver. Generation of oxidized forms of AmB (AmB-ox) in a patient's circulation may also generate ROS, causing side effects. Studies aimed at elimination of toxic properties of AmB are focused on forming complexes of AmB with copper(II) ions (AmB-Cu2+). However, the influence of such modified forms on renal cells and their transcriptome has not been studied so far. Therefore, the aim of this study was to answer the question of whether AmB-Cu2+ complexes and AmB-ox influence the transcriptional activity of melatonin-related and oxidative stress-related genes in human renal proximal tubule epithelial cells (RPTECs) and whether these changes can result in less toxicity of modified forms of AmB. Gene expression profile was evaluated with the use of oligonucleotide microarrays. At high concentrations AmB-Cu2+ was two times less toxic than AmB and AmB-ox. AmB-Cu2+ caused downregulation of oxidative stress-related genes and RORA, and upregulation of AANAT and MTNR1B. AmB-ox caused similar molecular changes. Based on cytotoxicity tests results and changes in melatonin- and oxidative stress-related genes expression profiles, we conclude that AmB-Cu2+ is less toxic for RPTECs.

Anahtar Kelimeler:

Amphotericin B, copper complexes, oxidative stress, melatonin, oligonucleotide microarrays

Expression profiles of genes related to melatonin and oxidative stress in human renal proximal tubule cells treated with antibiotic amphotericin B and its modified forms

Keywords:

Amphotericin B, copper complexes, oxidative stress, melatonin, oligonucleotide microarrays,

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Abraham P, Kolli VK, Rabi S (2010). Melatonin attenuates methotrexate-induced oxidative stress and renal damage in rats. Cell Biochem Funct 28: 426–433.
Antonowicz-Juchniewicz J, Jodkowska A, Kwiecińska D (2006). Secondary nephropathies in occupational health practice. II. Kidney disorders induced by drug and contrast media. Med Pr 57:455–468 (in Polish with abstract in English).
Brajtburg J, Elberg S, Kobayashi GS, Medoff G (1990). Inhibition of amphotericin B (Fungizone) toxicity to cells by egg lecithin-glycocholic acid mixed micelles. Antimicrob Agents Chemother 34: 2415–2416.
Brajtburg J, Elberg S, Schwartz DR, Vertut-Croquin A, Schlessinger D, Kobayashi GS, Medoff G (1985). Involvement of oxidative damage in erythrocyte lysis induced by amphotericin B. Antimicrob Agents Chemother 27: 172–176.
Bubenik GA (2002). Gastrointestinal melatonin: localization, function, and clinical relevance. Dig Dis Sci 47: 2336–2348.
Celik I, Cihangiroglu M, Ilhan N, Akpolat N, Akbulut HH (2005). Protective effects of different antioxidants and amrinone on vancomycin-induced nephrotoxicity. Basic Clin Pharmacol Toxicol 97: 325–332.
Chudzik B, Koselski M, Czuryło A, Trębacz K, Gagoś M (2015). A new look at the antibiotic amphotericin B effect on Candida albicans plasma membrane permeability and cell viability functions. Eur Biophys J 44: 77–90.
Chudzik B, Tracz IB, Czernel G, Fiołka MJ, Borsuk G, Gagoś M (2013). Amphotericin B-copper(II) complex as a potential agent with higher antifungal activity against Candida albicans. Eur J Pharm Sci 16; 49: 850–857.
Danielczyk K, Dzięgiel P (2009). MT1 melatonin receptors and their role in the oncostatic action of melatonin. Postepy Hig Med Dosw (Online) 63: 425–434 (in Polish with abstract in English).
Dupré SM, Dardente H, Birnie MJ, Loudon AS, Lincoln GA, Hazlerigg DG (2011). Evidence for RGS4 modulation of melatonin and thyrotrophin signalling pathways in the pars tuberalis. J Neuroendocrinol 23: 725–732.
Fazio EN, Dimattia GE, Chadi SA, Kernohan KD, Pin CL (2011). Stanniocalcin 2 alters PERK signaling and reduces cellular injury during cerulein induced pancreatitis in mice. BMC Cell Biology 12: 17.
Gagoś M, Arczewska M (2010). Spectroscopic studies of molecular organization of antibiotic amphotericin B in monolayers and dipalmitoylphosphatidylcholine lipid multibilayers. Biochim Biophys Acta 1798: 2124–2130.
Gagoś M, Czernel G, Kamiński DM, Kostro K (2011). Spectroscopic studies of amphotericin B-Cu2+ complexes. Biometals 24: 915– 922.
Gagoś M, Czernel G (2014). Oxidized forms of polyene antibiotic amphotericin B. Chem Phys Lett 598: 5–9.
Hossain MA, Maesaki S, Razzaque MS, Tomono K, Taguchi T, Kohno S (2000). Attenuation of nephrotoxicity by a novel lipid nanosphere (NS-718) incorporating amphotericin B. J Antimicrob Chemother 46: 263–268.
Hrenák J, Arendášová K, Rajkovičová R, Aziriová S, Repová K, Krajčírovičová K, Celec P, Kamodyová N, Bárta A, Adamcová M et al. (2013). Protective effect of captopril, olmesartan, melatonin and compound 21 on doxorubicin-induced nephrotoxicity in rats. Physiol Res 12: S181–189.
Ito D, Walker JR, Thompson CS, Moroz I, Lin W, Veselits ML, Hakim AM, Fienberg AA, Thinakaran G (2004). Characterization of stanniocalcin 2, a novel target of the mammalian unfolded protein response with cytoprotective properties. Mol Cell Biol 24: 9456–9469.
Ji M, Zhao WJ, Dong LD, Miao Y, Yang XL, Sun XH, Wang Z (2011). RGS2 and RGS4 modulate melatonin-induced potentiation of glycine currents in rat retinal ganglion cells. Brain Res 1411: 1–8.
Jiménez-Ortega V, Cano Barquilla P, Fernández-Mateos P, Cardinali DP, Esquifino AI (2012). Cadmium as an endocrine disruptor: correlation with anterior pituitary redox and circadian clock mechanisms and prevention by melatonin. Free Radic Biol Med 53: 2287–2297.
Lin ZY, Chuang WL (2010). Pharmacologic concentrations of melatonin have diverse influence on differential expressions of angiogenic chemokine genes in different hepatocellular carcinoma cell lines. Biomed Pharmacother 64: 659–662.
Lowes DA, Webster NR, Murphy MP, Galley HF (2013). Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis. Br J Anaesth 110: 472–480.
Madhu P, Reddy KP, Reddy PS (2015). Melatonin reduces oxidative stress and restores mitochondrial function in the liver of rats exposed to chemotherapeutics. J Exp Zool A Ecol Genet Physiol 323: 301–308.
Mangs AH, Speirs HJ, Goy C, Adams DJ, Markus MA, Morris BJ (2006). XE7: a novel splicing factor that interacts with ASF/SF2 and ZNF265. Nucleic Acids Res 34: 4976–4986.
Mesa-Arango AC, Scorzoni L, Zaragoza O (2012). It only takes one to do many jobs: Amphotericin B as antifungal and immunomodulatory drug. Front Microbiol 3: 286.
Nazıroğlu M, Yüksel M, Köse SA, Özkaya MO (2013). Recent reports of Wi-Fi and mobile phone-induced radiation on oxidative stress and reproductive signaling pathways in females and males. J Membr Biol 246: 869–875.
Ozbek E, Turkoz Y, Sahna E, Ozugurlu F, Mizrak B, Ozbek M (2000). Melatonin administration prevents the nephrotoxicity induced by gentamicin. BJU Int 85: 742–746.
Pandi-Perumal SR, Trakht I, Srinivasan V, Spence DW, Maestroni GJ, Zisapel N, Cardinali DP (2008). Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Prog Neurobiol 85: 335–353.
Parlakpinar H, Ozer MK, Sahna E, Vardi N, Cigremis Y, Acet A (2003). Amikacin-induced acute renal injury in rats: protective role of melatonin. J Pineal Res 35: 85–90.
Patel GP, Crank CW, Leikin JB (2011). An evaluation of hepatotoxicity and nephrotoxicity of liposomal amphotericin B (L-AMB). J Med Toxicol 7: 12–15.
Paulo CS, Lino MM, Matos AA, Ferreira LS (2013). Differential internalization of amphotericin B--conjugated nanoparticles in human cells and the expression of heat shock protein 70. Biomaterials 34: 5281–5293.
Ram PT, Dai J, Yuan L, Dong C, Kiefer TL, Lai L, Hill SM (2002). Involvement of the mt1 melatonin receptor in human breast cancer. Cancer Lett 179: 141–150.
Romero A, Ramos E, de Los Ríos C, Egea J, Del Pino J, Reiter RJ (2014). A review of metal-catalyzed molecular damage: protection by melatonin. J Pineal Res 56: 343–370.
Sansanwal P, Li L, Sarwal MM (2015). Inhibition of intracellular clusterin attenuates cell death in nephropathic cystinosis. J Am Soc Nephrol 26: 612–625.
Slominski AT, Tobin DJ, Zmijewski MA, Wortsman J, Paus R (2008). Melatonin in the skin: synthesis, metabolism and functions. Trends Endocrinol Metab 19: 17–24.
Slominski RM, Reiter RJ, Schlabritz-Loutsevitch N, Ostrom RS, Slominski AT (2012). Melatonin membrane receptors in peripheral tissues: distribution and functions. Mol Cell Endocrinol 351: 152–166.
Spampinato C, Leonardi D (2013). Candida infections, causes, targets, and resistance mechanisms: traditional and alternative antifungal agents. Biomed Res Int 2013: 204–237.
Stępniewska J, Gołembiewska E, Dołęgowska B, Domański M, Ciechanowski K (2015). Oxidative stress and antioxidative enzyme activities in chronic kidney disease and different types of renal replacement therapy. Curr Protein Pept Sci 16: 243– 248.
Tan DX, Manchester LC, Hardeland R, Lopez-Burillo S, Mayo JC, Sainz RM, Reiter RJ (2003). Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. J Pineal Res 34: 75–78.
Witt-Enderby PA, Jarzynka MJ, Krawitt BJ, Melan MA (2004). Knock- down of RGS4 and beta tubulin in CHO cells expressing the human MT1 melatonin receptor prevents melatonin-induced receptor desensitization. Life Sci 75: 2703–2715.
Yürüker V, Nazıroğlu M, Şenol N (2015). Reduction in traumatic brain injury-induced oxidative stress, apoptosis, and calcium entry in rat hippocampus by melatonin: Possible involvement of TRPM2 channels. Metab Brain Dis 30: 223–231.