The effect of renalase-derived peptides on viability of HepG₂ and PC3 cells

Fedchenko V.I.1, Morozevich G.E.1, Medvedev A.E.1

1. Institute of Biomedical Chemistry, Moscow, Russia
Section: Short Communication
DOI: 10.18097/PBMC20236903184      PubMed Id: 37384910
Year: 2023  Volume: 69  Issue: 3  Pages: 184-187
Renalase (RNLS) is a recently discovered protein, which plays different roles inside and outside cells. Intracellular RNLS is a FAD-dependent oxidoreductase (EC, while extracellular RNLS lacks its N-terminal peptide, FAD cofactor, and exhibits various protective effects in a non-catalytic manner. Certain evidence exists, that plasma/serum RNLS is not an intact protein secreted into the extracellular space, and exogenous recombinant RNLS is effectively degraded during short-term incubation with human plasma samples. Some synthetic analogues of the RNLS sequence (e.g. the Desir's peptide RP-220, a 20-mer peptide corresponding to the RNLS sequence 220–239) have effects on cell survival. This suggests that RNLS-derived peptides, formed during proteolytic processing, may have own biological activity. Based on results of a recent bioinformatics analysis of potential cleavage sites of RNLS (Fedchenko et al., Medical Hypotheses, 2022) we have investigated the effect of four RNLS-derived peptides as well as RP-220 and its fragment (RP-224) on the viability of two cancer cell lines: HepG₂ (human hepatoma) and PC3 (prostate cancer). Two RNLS-derived peptides (RP-207 and RP-220) decreased the viability of HepG₂ cells in a concentration dependent manner. The most pronounced and statistically significant effect (30–40% inhibition of cell growth) was observed at 50 μM concentration of each peptide. In the experiments with PC3 cells five of six RNLS-derived peptides had a significant impact on the cell viability. RP-220 and RP-224 decreased cell viability; however, no concentration dependence of this effect was observed in the range of concentrations studied (1–50 μM). Three other RNLS-derived peptides (RP-207, RP-233, and RP-265) increased viability of PC3 cells by 20–30%, but no concentration-dependence of this effect was found. Data obtained suggest that some RNLS-derived peptides may influence the viability of various cells and manifestation and direction of the effect (increase of decrease of the cell viability) is cell-type-specific.
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Keywords: renalase (RNLS), RNLS-derived peptides, cell viability, HepG2 and PC3 cells

Fedchenko, V. I., Morozevich, G. E., Medvedev, A. E. (2023). The effect of renalase-derived peptides on viability of HepG₂ and PC3 cells. Biomeditsinskaya Khimiya, 69(3), 184-187.
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