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INT RO DUCT ION: The main limitation of the use of amphotericin B (AmB) – effective in the treatment of systemic fungal infections – is its high toxicity to human cells. The mechanism of AmB toxicity is not clear. Caspase-related and BCL-2 proteins participate in the regulation of apoptosis. Thus, they may be involved in drug toxicity. In this study we evaluated the influence of AmB on the transcriptional activity of genes related to caspases and the BCL-2 family. We also tested the influence of modified forms of AmB: AmB-Cu 2+ (the complex with copper(II) ions) and the AmB-ox (oxidized form). MAT ERIAL AND MET HO DS : Human RPTECs (Renal Proximal Tubule Epithelial Cells) were treated with AmB, AmB-Cu 2+ and AmB-ox. Total RNA was extracted using the phenol-chloroform method. The expression profiles of genes related to caspase activity and BCL-2 were determined using oligonucleotide microarrays (HG-U133A 2.0, Affymetrix). Analysis included 67 ID related to caspases and 32 ID associated with BCL-2, according to the Affymetrix database. RES ULTS : The analysis revealed upregulation of the BCL-2 and BCL2L1genes in the cells treated with AmB-Cu 2+ , in comparison to the control. In both the AmB and AmB-Cu 2+ -treated cells, differentiating genes were associated with inflammation and mitophagy activated by intrinsic signals. In the cells treated with AmB-ox, the BCL-2 genes were downregulated. CO NCL US IO NS : The results suggest that AmB and AmB-Cu activate genes involved in the regulation of inflammation and autophagy induced by intrinsic signals, but overexpression of BCL-2 and BCL2L1 may protect AmB-Cu 2+ -treated cells from death. In the cells treated with AmB-ox extrinsic signals prevail, indicating the distinct molecular mechanism of its cytotoxicity. Received: 24.01.2017 Revised: 23.07.2017 Accepted: 24.07.2017 Published online: 26.03.2018 Address for correspondence: Dr n. med. Joanna Gola, Katedra i Zakład Biologii Molekularnej, Wydział Farmaceutyczny z Oddziałem Medycyny Laboratoryjnej w Sosnowcu, Śląski Uniwersytet Medyczny w Katowicach, ul. Jedności 8, 41-200 Sosnowiec, tel. tel. + 48 32 364 10 27, e-mail: jgola@sum.edu.pl Copyright © Śląski Uniwersytet Medyczny w Katowicach www.annales.sum.edu.pl J.M. Gola i wsp.: INFLUENCE OF AmB ON CASPASES AND BCL-2 EXPRESSION

Changes in expression of genes related to caspases and BCL-2 family in RPTEC treated with amphotericin B and its modified forms