renrenase衍生肽对HepG 2和PC3细胞活力的影响。

Q3 Biochemistry, Genetics and Molecular Biology Biomeditsinskaya khimiya Pub Date : 2023-06-01 DOI:10.18097/PBMC20236903184

V I Fedchenko, G E Morozevich, A E Medvedev

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引用次数: 0

摘要

Renalase (RNLS)是一种新发现的蛋白，在细胞内外起着不同的作用。细胞内RNLS是FAD依赖的氧化还原酶(EC 1.6.3.5)，而细胞外RNLS缺乏其n端肽、FAD辅因子，以非催化方式表现出各种保护作用。有证据表明，血浆/血清RNLS并不是一种分泌到细胞外空间的完整蛋白，外源性重组RNLS在与人血浆样品的短期孵育过程中可以有效降解。一些RNLS序列的合成类似物(如Desir的肽RP-220，一种与RNLS序列220-239对应的20聚体肽)对细胞存活有影响。这表明在蛋白质水解过程中形成的rnls衍生肽可能具有自身的生物活性。基于最近对RNLS潜在切割位点的生物信息学分析结果(Fedchenko et al.， Medical hypothesis, 2022)，我们研究了四种RNLS衍生肽以及RP-220及其片段(RP-224)对两种癌细胞系HepG₂(人肝癌)和PC3(前列腺癌)活力的影响。两种rnls衍生肽(RP-207和RP-220)以浓度依赖的方式降低HepG 2细胞的活力。在每个肽浓度为50 μM时，观察到最明显且具有统计学意义的效果(30-40%的细胞生长抑制)。在PC3细胞实验中，六种rnls衍生肽中有五种对细胞活力有显著影响。RP-220和RP-224降低细胞活力;然而，在研究的浓度范围(1-50 μM)内，没有观察到这种效应的浓度依赖性。另外三种rnls衍生肽(RP-207、RP-233和RP-265)可使PC3细胞的活力提高20-30%，但没有发现这种作用的浓度依赖性。结果表明，一些rnls衍生的多肽可能影响多种细胞的活力，且这种影响的表现和方向(细胞活力的增加或降低)具有细胞类型特异性。

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

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.

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来源期刊

Biomeditsinskaya khimiya Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

1.30

自引率

0.00%

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期刊介绍： The aim of the Russian-language journal "Biomeditsinskaya Khimiya" (Biomedical Chemistry) is to introduce the latest results obtained by scientists from Russia and other Republics of the Former Soviet Union. The Journal will cover all major areas of Biomedical chemistry, including neurochemistry, clinical chemistry, molecular biology of pathological processes, gene therapy, development of new drugs and their biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine etc. The Journal also publish review articles. All issues of journal usually contain invited reviews. Papers written in Russian contain abstract (in English).