Renalase (RNLS) is a recently discovered protein, which plays different roles inside and outside cells. Intracellular RNLS is a FAD-dependent oxidoreductase (EC 1.6.3.5), 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.
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.
Fedchenko V.I. et al. The effect of renalase-derived peptides on viability of HepG₂ and PC3 cells // Biomeditsinskaya Khimiya. - 2023. - V. 69. -N 3. - P. 184-187.
Fedchenko V.I. et al., "The effect of renalase-derived peptides on viability of HepG₂ and PC3 cells." Biomeditsinskaya Khimiya 69.3 (2023): 184-187.
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.
References
Xu J., Li G., Wang P., Velazquez H., Yao X., Li Y., Wu Y., Peixoto A., Crowley S., Desir G.V. (2005) Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure. J. Clin. Invest., 115(5), 1275-1280. CrossRef Scholar google search
Medvedev A.E., Veselovsky A.V., Fedchenko V.I. (2010) Renalase, a new secretory enzyme responsible for selective degradation of catecholamines: Achievements and unsolved problems. Biochemistry (Moscow), 75(8), 951-958. CrossRef Scholar google search
Baroni S., Milani M., Pandini V., Pavesi G., Horner D., Aliverti A. (2013) Is renalase a novel player in catecholaminergic signaling? The mystery of the catalytic activity of an intriguing new flavoenzyme. Curr. Pharm. Des., 19, 2540-2551. CrossRef Scholar google search
Desir G.V., Peixoto A.J. (2014) Renalase in hypertension and kidney disease. Nephrol. Dial. Transplant., 29(1), 22-28. CrossRef Scholar google search
Moran G.R. (2016) The catalytic function of renalase: A decade of phantoms. Biochim. Biophys. Acta, 1864(1), 177-186. CrossRef Scholar google search
Beaupre B.A., Hoag M.R., Roman J., Forsterling F.H., Moran G.R. (2015) Metabolic function for human renalase: Oxidation of isomeric forms of beta-NAD(P)H that are inhibitory to primary metabolism. Biochemistry, 54(3), 795-806. Scholar google search
Milani M., Ciriello F., Baroni S., Pandini V., Canevari G., Bolognesi M., Aliverti A. (2011) FAD-binding site and NADP reactivity in human renalase: A new enzyme involved in blood pressure regulation. J. Mol. Biol., 411(2), 463-473. CrossRef Scholar google search
Fedchenko V.I., Buneeva O.A., Kopylov A.T., Veselovsky A.V., Zgoda V.G., Medvedev A.E. (2015) Human urinary renalase lacks the N-terminal signal peptide crucial for accommodation of its FAD cofactor. Int. J. Biol. Macromol., 78, 347-353. CrossRef Scholar google search
Fedchenko V., Kopylov A., Kozlova N., Buneeva O., Kaloshin A., Zgoda V., Medvedev A. (2016) Renalase secreted by human kidney HEK293T cells lacks its N-terminal peptide: Implications for putative mechanisms of renalase action. Kidney Blood Press. Res., 41, 593-603. CrossRef Scholar google search
Wang Y., Safirstein R., Velazquez H., Guo X.J., Hollander L., Chang J., Chen T.M., Mu J.J., Desir G.V. (2017) Extracellular renalase protects cells and organs by outside-in signalling. J. CellMol. Med., 21(7), 1260-1265. CrossRef Scholar google search
Kolodecik T.R., Reed A.M., Date K., Shugrue C.A., Patel V., Chung S.L., Desir G.V., Gorelick, F.S. (2017) The serum protein renalase reduces injury in experimental pancreatitis. J. Biol. Chem., 292(51), 21047-21059. CrossRef Scholar google search
Wang L., Velazquez H., Chang J., Safirstein R., Desir G.V. (2015) Identification of a receptor for extracellular renalase. PLoS One, 10, e0122932. CrossRef Scholar google search
Pointer T.C., Gorelick F.S., Desir G.V. (2021) Renalase: A multi-functional signaling molecule with roles in gastrointestinal disease, Cells, 10, 2006. CrossRef Scholar google search
Kopylov A.T., Fedchenko V.I., Buneeva O.A., Pyatakova N.V., Zgoda V.G., Medvedev A.E. (2018) A new method for quantitative determination of renalase based on mass spectrometric determination of a proteotypic peptide labelled with stable isotopes, Rapid Commun. Mass Spectrom., 32, 1263-1270. CrossRef Scholar google search
Medvedev A., Kopylov A., Fedchenko V., Buneeva O. (2020) Is renalase ready to become a biomarker of ischemia? Int. J. Cardiol., 307, 179. CrossRef Scholar google search
Fedchenko V.I., Veselovsky A.V., Kopylov A.T., Kaloshina S.A., Medvedev A.E. (2022) Renalase may be cleaved in blood. Are blood chymotrypsin-like enzymes involved? Medical Hypotheses, 165, 110895. CrossRef Scholar google search
Morozevich G.E., Kozlova N.I., Susova O.Y., Lupatov A.Y., Berman A.E. (2017) Hyperexpression of integrin α5β1 promotes resistance of MCF-7 human breast carcinoma cells to doxorubicin via ERK protein kinase down-regulation. Biochemistry (Moscow), 82(9), 1017-1024. CrossRef Scholar google search
