21 research outputs found
Specific Characteristics of a Sports Column in Russian and Foreign Sports Mass Communication Outlets
This article points out similarities and differences of sports columns in modern Russian and foreign sports mass communication outlets. Empirical base of our research are texts from championat.com, newspaper Β«Π‘ΠΏΠΎΡΡ-ΠΠΊΡΠΏΡΠ΅ΡΡΒ» and some foreign sports mass communication outlets. All the translations from English to Russian are made by the author of the article. Original texts of interviews of experts in the matter. Scientific value of this article is that authors implicates new scientific terminology on the matter of sports columns.Π Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΠ΅ ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°ΡΡΡΡ ΡΡ
ΠΎΠ΄ΡΡΠ²Π° ΠΈ ΡΠ°Π·Π»ΠΈΡΠΈΡ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»ΠΎΠ² ΠΆΠ°Π½ΡΠ° ΡΠΏΠΎΡΡΠΈΠ²Π½ΠΎΠΉ ΠΊΠΎΠ»ΠΎΠ½ΠΊΠ΅ Π² ΠΏΡΠ°ΠΊΡΠΈΠΊΠ΅ ΡΠΎΡΡΠΈΠΉΡΠΊΠΈΡ
ΠΈ Π·Π°ΡΡΠ±Π΅ΠΆΠ½ΡΡ
ΡΠΏΠΎΡΡΠΈΠ²Π½ΡΡ
ΡΡΠ΅Π΄ΡΡΠ² ΠΌΠ°ΡΡΠΎΠ²ΠΎΠΉ ΠΈΠ½ΡΠΎΡΠΌΠ°ΡΠΈΠΈ. ΠΠΌΠΏΠΈΡΠΈΡΠ΅ΡΠΊΡΡ Π±Π°Π·Ρ Π½Π°ΡΠ΅Π³ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΡΠΎΡΡΠ°Π²ΠΈΠ»ΠΈ ΠΏΡΠ±Π»ΠΈΠΊΠ°ΡΠΈΠΈ ΠΏΠΎΡΡΠ°Π»Π° championat.com, Π³Π°Π·Π΅ΡΡ Β«Π‘ΠΏΠΎΡΡ-ΠΠΊΡΠΏΡΠ΅ΡΡΒ» Π° ΡΠ°ΠΊΠΆΠ΅ Π½Π΅ΡΠΊΠΎΠ»ΡΠΊΠΈΡ
Π·Π°ΡΡΠ±Π΅ΠΆΠ½ΡΡ
Π‘ΠΠ. ΠΡΠ΅ ΠΏΠ΅ΡΠ΅Π²ΠΎΠ΄Ρ ΠΏΠ΅ΡΠ²ΠΎΠΈΡΡΠΎΡΠ½ΠΈΠΊΠΎΠ² Ρ Π°Π½Π³Π»ΠΈΠΉΡΠΊΠΎΠ³ΠΎ ΡΠ·ΡΠΊΠ° Π²ΡΠΏΠΎΠ»Π½Π΅Π½Ρ Π°Π²ΡΠΎΡΠΎΠΌ ΡΡΠ°ΡΡΠΈ. ΠΡΠΈ Π½Π°ΠΏΠΈΡΠ°Π½ΠΈΠΈ ΡΠ°Π±ΠΎΡΡ Π°Π²ΡΠΎΡ ΠΎΠΏΠΈΡΠ°Π»ΡΡ Π½Π° ΠΎΡΠΈΠ³ΠΈΠ½Π°Π»Ρ ΠΈΠ½ΡΠ΅ΡΠ²ΡΡ ΠΈ Π±Π΅ΡΠ΅Π΄Ρ Ρ ΡΠΊΡΠΏΠ΅ΡΡΠ°ΠΌΠΈ. ΠΠ°ΡΡΠ½Π°Ρ Π·Π½Π°ΡΠΈΠΌΠΎΡΡΡ ΡΠ°Π±ΠΎΡΡ ΡΠΎΡΡΠΎΠΈΡ Π² ΡΠΎΠΌ, ΡΡΠΎ Π°Π²ΡΠΎΡΠΎΠΌ Π±ΡΠ»ΠΈ Π² Π²Π΅Π΄Π΅Π½Ρ Π² Π½Π°ΡΡΠ½ΡΠΉ ΠΎΠ±ΠΎΡΠΎΡ Π½ΠΎΠ²ΡΠ΅ ΠΏΠΎΠ½ΡΡΠΈΡ ΠΈ ΡΠ΅ΡΠΌΠΈΠ½Ρ, ΡΠ²ΡΠ·Π°Π½Π½ΡΠ΅ ΡΠΎ ΡΠΏΠΎΡΡΠΈΠ²Π½ΠΎΠΉ ΠΊΠΎΠ»ΡΠΌΠ½ΠΈΡΡΠΈΠΊΠΎΠΉ
Different metastasis promotive potency of small G-proteins RalA and RalB in in vivo hamster tumor model
<p>Abstract</p> <p>Background</p> <p>Previously we have shown that oncogenic Ha-Ras stimulated <it>in vivo </it>metastasis through RalGEF-Ral signaling. RalA and RalB are highly homologous small G proteins belonging to Ras superfamily. They can be activated by Ras-RalGEF signaling pathway and influence cellular growth and survival, motility, vesicular transport and tumor progression in humans and in animal models. Here we first time compared the influence of RalA and RalB on tumorigenic, invasive and metastatic properties of RSV transformed hamster fibroblasts.</p> <p>Methods</p> <p>Retroviral vectors encoding activated forms or effector mutants of RalA or RalB proteins were introduced into the low metastatic HET-SR cell line. Tumor growth and spontaneous metastatic activity (SMA) were evaluated on immunocompetent hamsters after subcutaneous injection of cells. The biological properties of cells, including proliferation, clonogenicity, migration and invasion were determined using MTT, wound healing, colony formation and Boyden chamber assays respectively. Protein expression and phosphorylation was detected by Westen blot analysis. Extracellular proteinases activity was assessed by substrate-specific zymography.</p> <p>Results</p> <p>We have showed that although both Ral proteins stimulated SMA, RalB was more effective in metastasis stimulation <it>in vivo </it>as well as in potentiating of directed movement and invasion <it>in vitro</it>. Simultaneous expression of active RalA and RalB didn't give synergetic effect on metastasis formation. RalB activity decreased expression of Caveolin-1, while active RalA stimulated MMP-1 and uPA proteolytic activity, as well as CD24 expression. Both Ral proteins were capable of Cyclin D1 upregulation, JNK1 kinase activation, and stimulation of colony growth and motility. Among three main RalB effectors (RalBP1, exocyst complex and PLD1), PLD1 was essential for RalB-dependent metastasis stimulation.</p> <p>Conclusions</p> <p>Presented results are the first data on direct comparison of RalA and RalB impact as well as of RalA/RalB simultaneous expression influence on <it>in vivo </it>cell metastatic activity. We showed that RalB activation significantly more than RalA stimulates SMA. This property correlates with the ability of RalB to stimulate <it>in vitro </it>invasion and serum directed cell movement. We also found that RalB-PLD1 interaction is necessary for the acquisition of RalB-dependent high metastatic cell phenotype. These findings contribute to the identification of molecular mechanisms of metastasis and tumor progression.</p
The role of nano-perovskite in the negligible thorium release in seawater from Greek bauxite residue (red mud)
We present new data about the chemical and structural characteristics of bauxite residue (BR) from Greek Al industry, using a combination of microscopic, analytical, and spectroscopic techniques. SEM-EDS indicated a homogeneous dominant βAl-Fe-Ca-Ti-Si-Na-Cr matrixβ, appearing at the microscale. The bulk chemical analyses showed considerable levels of Th (111βΞΌg gβ1), along with minor U (15βΞΌg gβ1), which are responsible for radioactivity (355 and 133βBq kgβ1 for 232Th and 238U, respectively) with a total dose rate of 295βnGy hβ1. Leaching experiments, in conjunction with SF-ICP-MS, using Mediterranean seawater from Greece, indicated significant release of V, depending on S/L ratio, and negligible release of Th at least after 12 months leaching. STEM-EDS/EELS & HR-STEM-HAADF study of the leached BR at the nanoscale revealed that the significant immobility of Th4+ is due to its incorporation into an insoluble perovskite-type phase with major composition of Ca0.8Na0.2TiO3 and crystallites observed in nanoscale. The Th LIII-edge EXAFS spectra demonstrated that Th4+ ions, which are hosted in this novel nano-perovskite of BR, occupy Ca2+ sites, rather than Ti4+ sites. That is most likely the reason of no Th release in Mediterranean seawater
Π‘ΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΡ ΠΊ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π΄ΡΠΏΠ»Π΅ΠΊΡΠΎΠ² ΠΊΠ°ΠΊ ΡΠ°ΠΊΡΠΎΡ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ°ΡΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΠΌΠΈΠΊΡΠΎΠ ΠΠ
Background. The regulation of the content of mature microRNAs (miRNAs) in different cell compartments β the nucleus (N) and the cytoplasm (C) β makes it possible to control their availability for participation in RNA-mediated interference processes. Structurally different miRNAs, processed from different precursors (pre-miRNA), can form duplexes between molecules containing complementary sequences. The appearance of such duplexes can be considered as one of the mechanisms of miRNA activity regulation in respect to their target mRNAs. Objectives. Analysis of the miRNA distribution between nucleus and cytoplasm depending on the energy of duplex formation. Materials and methods. Data on the content of different miRNAs in the nucleus and cytoplasm in two cell lines of different origin: 5-8F of human nasopharyngeal carcinoma (NPC) and postmitotic neurons of the cerebral cortex of rat β has been used. The miRNA sequences used for analysis were taken from the miRBase database, version 22. Bioinformatic analysis of miRNA sequences for detection of molecules capable of forming miRNA duplexes and determination of their minimal free energy (MFE) of formation was carried out with the help of programs: RegRNA, version 2.0, and RNAup.Β Results. For the first time, a comparative analysis of the intracellular distribution N/C of different miRNAs depending on the energy of duplex formation was performed. Results of bioinformatic analysis of miRNA sequencing in 5-8F cells of human nasopharyngeal carcinoma showed that miRNAs capable of forming high-energy, i. e. more stable, duplexes, accumulate in the cytoplasm, while miRNAs forming low-energy duplexes have a larger N/C value, i. e. the level of these miRNAs is higher in the nucleus. In addition, we show that N/C distribution of miRNAs capable of forming high-energy duplexes is independent from the presence of certain short motifs, that are supposedly associated with their nuclear localization. Conclusion. The revealed enrichment of the pool of cytoplasmic miRNAs by molecules capable of forming more energetically stable duplexes may represent an additional mechanism of regulating miRNA activity in respect to their target mRNAs due to the sequestration of miRNA duplexes in the cytoplasm preventing miRNA interaction with mRNAs.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. Π Π΅Π³ΡΠ»ΡΡΠΈΡ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΡ Π·ΡΠ΅Π»ΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ (ΠΌΠΈΠ ΠΠ) Π² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΊΠΎΠΌΠΏΠ°ΡΡΠΌΠ΅Π½ΡΠ°Ρ
ΠΊΠ»Π΅ΡΠΊΠΈ β ΡΠ΄ΡΠ΅ (N) ΠΈ ΡΠΈΡΠΎΠΏΠ»Π°Π·ΠΌΠ΅ (C) β ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΠΊΠΎΠ½ΡΡΠΎΠ»ΠΈΡΠΎΠ²Π°ΡΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΠΈΡ
ΡΡΠ°ΡΡΠΈΡ Π² ΠΏΡΠΎΡΠ΅ΡΡΠ°Ρ
Π ΠΠ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ ΠΈΠ½ΡΠ΅ΡΡΠ΅ΡΠ΅Π½ΡΠΈΠΈ. Π Π°Π·Π»ΠΈΡΠ½ΡΠ΅ ΠΏΠΎ ΡΡΡΡΠΊΡΡΡΠ΅ ΠΌΠΈΠ ΠΠ, ΠΏΡΠΎΡΠ΅ΡΡΠΈΠ½Π³ ΠΊΠΎΡΠΎΡΡΡ
ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΠ΅ΡΡΡ Ρ ΡΠ°Π·Π½ΡΡ
ΠΏΡΠ΅Π΄ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΈΠΊΠΎΠ² (ΠΏΡΠ΅-ΠΌΠΈΠ ΠΠ), ΠΌΠΎΠ³ΡΡ ΠΎΠ±ΡΠ°Π·ΠΎΠ²ΡΠ²Π°ΡΡ Π΄ΡΠΏΠ»Π΅ΠΊΡΡ ΠΌΠ΅ΠΆΠ΄Ρ ΠΌΠΎΠ»Π΅ΠΊΡΠ»Π°ΠΌΠΈ ΠΏΡΠΈ Π½Π°Π»ΠΈΡΠΈΠΈ Π² Π½ΠΈΡ
ΠΊΠΎΠΌΠΏΠ»Π΅ΠΌΠ΅Π½ΡΠ°ΡΠ½ΡΡ
ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠ΅ΠΉ. Π€ΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠ°ΠΊΠΈΡ
Π΄ΡΠΏΠ»Π΅ΠΊΡΠΎΠ² ΠΌΠΎΠΆΠ΅Ρ ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°ΡΡΡΡ ΠΊΠ°ΠΊ ΠΎΠ΄ΠΈΠ½ ΠΈΠ· ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠ² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΌΠΈΠ ΠΠ Π² ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠΈ ΠΈΡ
ΡΠ°ΡΠ³Π΅ΡΠ½ΡΡ
ΠΌΠ°ΡΡΠΈΡΠ½ΡΡ
Π ΠΠ (ΠΌΠ ΠΠ). Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β Π°Π½Π°Π»ΠΈΠ· ΡΠ°ΡΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΌΠΈΠ ΠΠ ΠΌΠ΅ΠΆΠ΄Ρ ΡΠ΄ΡΠΎΠΌ ΠΈ ΡΠΈΡΠΎΠΏΠ»Π°Π·ΠΌΠΎΠΉ Π² Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ ΡΠ½Π΅ΡΠ³ΠΈΠΈ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΡ Π΄ΡΠΏΠ»Π΅ΠΊΡΠΎΠ². ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΠ°ΡΠ΅ΡΠΈΠ°Π»ΠΎΠΌ Π΄Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΠΎΡΠ»ΡΠΆΠΈΠ»ΠΈ Π΄Π°Π½Π½ΡΠ΅ ΠΎ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΌΠΈΠ ΠΠ Π² ΡΠ΄ΡΠ΅ ΠΈ ΡΠΈΡΠΎΠΏΠ»Π°Π·ΠΌΠ΅ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ
2 Π»ΠΈΠ½ΠΈΠΉ ΡΠ°Π·Π»ΠΈΡΠ½ΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΡΡ
ΠΎΠΆΠ΄Π΅Π½ΠΈΡ: 5-8F Π½Π°Π·ΠΎΡΠ°ΡΠΈΠ½Π³Π΅Π°Π»ΡΠ½ΠΎΠΉ ΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌΡ (nasopharyngeal carcinoma, NPC) ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° ΠΈ ΠΏΠΎΡΡΠΌΠΈΡΠΎΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π½Π΅ΠΉΡΠΎΠ½ΠΎΠ² ΠΊΠΎΡΡ Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π° ΡΠ΅ΡΠΎΠΉ ΠΊΡΡΡΡ. ΠΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΌΠΈΠ ΠΠ, ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΠΌΡΠ΅ Π΄Π»Ρ Π°Π½Π°Π»ΠΈΠ·Π°, Π±ΡΠ»ΠΈ Π²Π·ΡΡΡ ΠΈΠ· Π±Π°Π·Ρ Π΄Π°Π½Π½ΡΡ
miRBase, Π²Π΅ΡΡΠΈΡ 22. ΠΠΈΠΎΠΈΠ½ΡΠΎΡΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠ΅ΠΉ ΠΌΠΈΠ ΠΠ Π΄Π»Ρ Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ ΠΌΠΎΠ»Π΅ΠΊΡΠ», ΡΠΏΠΎΡΠΎΠ±Π½ΡΡ
ΠΎΠ±ΡΠ°Π·ΠΎΠ²ΡΠ²Π°ΡΡ Π΄ΡΠΏΠ»Π΅ΠΊΡΡ ΠΌΠΈΠ ΠΠ, ΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΠΌΠΈΠ½ΠΈΠΌΠ°Π»ΡΠ½ΠΎΠΉ ΡΠ²ΠΎΠ±ΠΎΠ΄Π½ΠΎΠΉ ΡΠ½Π΅ΡΠ³ΠΈΠΈ (minimum free energy, MFE) ΠΈΡ
ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ c ΠΏΠΎΠΌΠΎΡΡΡ ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΌ RegRNA, Π²Π΅ΡΡΠΈΡ 2.0, ΠΈ RNAup. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΠΏΠ΅ΡΠ²ΡΠ΅ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ ΡΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ°ΡΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ (ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠ΅ N/C) ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΌΠΈΠ ΠΠ Π² Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ ΡΠ½Π΅ΡΠ³ΠΈΠΈ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΡ Π΄ΡΠΏΠ»Π΅ΠΊΡΠΎΠ². Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ Π±ΠΈΠΎΠΈΠ½ΡΠΎΡΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π° Π΄Π°Π½Π½ΡΡ
ΡΠ΅ΠΊΠ²Π΅Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΌΠΈΠ ΠΠ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ
Π»ΠΈΠ½ΠΈΠΈ 5-8F NPC ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ, ΡΡΠΎ ΠΌΠΈΠ ΠΠ, ΡΠΏΠΎΡΠΎΠ±Π½ΡΠ΅ ΠΎΠ±ΡΠ°Π·ΠΎΠ²ΡΠ²Π°ΡΡ Π²ΡΡΠΎΠΊΠΎΡΠ½Π΅ΡΠ³Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅, Ρ. Π΅. Π±ΠΎΠ»Π΅Π΅ ΡΡΠ°Π±ΠΈΠ»ΡΠ½ΡΠ΅, Π΄ΡΠΏΠ»Π΅ΠΊΡΡ, Π½Π°ΠΊΠ°ΠΏΠ»ΠΈΠ²Π°ΡΡΡΡ Π² ΡΠΈΡΠΎΠΏΠ»Π°Π·ΠΌΠ΅, Π² ΡΠΎ Π²ΡΠ΅ΠΌΡ ΠΊΠ°ΠΊ Π½ΠΈΠ·ΠΊΠΎΡΠ½Π΅ΡΠ³Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Π΄ΡΠΏΠ»Π΅ΠΊΡΡ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ
Π΄Π°Π½Π½ΠΎΠΉ Π»ΠΈΠ½ΠΈΠΈ Π½Π°ΠΊΠ°ΠΏΠ»ΠΈΠ²Π°ΡΡΡΡ Π² ΡΠ΄ΡΠ΅ (ΠΈΠΌΠ΅ΡΡ Π±ΠΎΠ»ΡΡΠ΅Π΅ Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ N/C). Π’Π°ΠΊΠΆΠ΅ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ ΠΎΡΡΡΡΡΡΠ²ΠΈΠ΅ Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΡΠ°ΡΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ N/C ΠΎΡ ΡΡΠ΄Π° ΠΊΠΎΡΠΎΡΠΊΠΈΡ
ΠΌΠΎΡΠΈΠ²ΠΎΠ², ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠΈΡΠ΅Π»ΡΠ½ΠΎ Π°ΡΡΠΎΡΠΈΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Ρ ΡΠ΄Π΅ΡΠ½ΠΎΠΉ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΠ΅ΠΉ Π΄Π»Ρ ΠΌΠΈΠ ΠΠ, ΡΠΏΠΎΡΠΎΠ±Π½ΡΡ
ΠΎΠ±ΡΠ°Π·ΠΎΠ²ΡΠ²Π°ΡΡ Π²ΡΡΠΎΠΊΠΎΡΠ½Π΅ΡΠ³Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Π΄ΡΠΏΠ»Π΅ΠΊΡΡ. ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΡΡΠ²Π»Π΅Π½Π½ΠΎΠ΅ ΠΎΠ±ΠΎΠ³Π°ΡΠ΅Π½ΠΈΠ΅ ΠΏΡΠ»Π° ΡΠΈΡΠΎΠΏΠ»Π°Π·ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΌΠΈΠ ΠΠ ΠΌΠΎΠ»Π΅ΠΊΡΠ»Π°ΠΌΠΈ, ΡΠΏΠΎΡΠΎΠ±Π½ΡΠΌΠΈ ΠΎΠ±ΡΠ°Π·ΠΎΠ²ΡΠ²Π°ΡΡ Π±ΠΎΠ»Π΅Π΅ ΡΠ½Π΅ΡΠ³Π΅ΡΠΈΡΠ΅ΡΠΊΠΈ ΡΡΠ°Π±ΠΈΠ»ΡΠ½ΡΠ΅ Π΄ΡΠΏΠ»Π΅ΠΊΡΡ, ΠΌΠΎΠΆΠ΅Ρ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΡΡ Π΄ΠΎΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»ΡΠ½ΡΠΉ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΌΠΈΠ ΠΠ Π² ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠΈ ΠΈΡ
ΡΠ°ΡΠ³Π΅ΡΠ½ΡΡ
ΠΌΠ ΠΠ (Π·Π° ΡΡΠ΅Ρ ΡΠ΅ΠΊΠ²Π΅ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΌΠΈΠ ΠΠ Π² ΡΠΈΡΠΎΠΏΠ»Π°Π·ΠΌΠ΅ Π² ΡΠΎΡΡΠ°Π²Π΅ Π΄ΡΠΏΠ»Π΅ΠΊΡΠΎΠ², ΠΏΡΠ΅ΠΏΡΡΡΡΠ²ΡΡΡΠΈΡ
Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΌΠΈΠ ΠΠ Ρ ΠΌΠ ΠΠ)
ΠΠ»ΠΈΡΠ½ΠΈΠ΅ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ CRABP1 Π½Π° ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΡ ΠΈ ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΠΊ ΡΠ΅ΡΠΈΠ½ΠΎΠ΅Π²ΠΎΠΉ ΠΊΠΈΡΠ»ΠΎΡΠ΅ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΡΡ ΠΎΠΆΠ΄Π΅Π½ΠΈΡ
Background. Retinoic acid (RA), by modulation of the transcription of a number of retinoid-responsive genes, is involved in the regulation of cell differentiation and proliferation. The mechanisms by which the RA-binding proteins, molecular chaperones CRABP1 and CRABP2 (Cellular Retinoic Acid Proteins-1 and -2), participate in the realization of RA activity, as well as their precise role in tumor progression are still not fully understood. Recent data indicate that functional differences of CRABP proteins with respect to malignization of breast cancer cells could be determined by different sensitivity of tumor cells to RA and with the receptor status of the tumor.Materials and methods. The CRABP1 coding sequence was overexpressed in breast cancer cells without endogenous expression of this protein, with different levels of RA sensitivity and receptor status β SKBR3 (RA-sensitive, ER(β) / HER2(+) cells) and MDA-MB-231 (RA-resistant, triple negative status). The growth of CRABP1(+) derivatives and control cells was evaluated under standard culture conditions and in the presence of various concentrations of RA.Results. The effect of CRABP1 expression in RA-sensitive and RA-resistant breast cancer cells with different receptor status on the growth rate and sensitivity of cells to RA was studied. The expression of CRABP1 in RA-sensitive SKBR3 cells enhances proliferation in the absence of RA and decreases the antiproliferative effect of RA, while in RA-resistant triple-negative MDA-MB-231 cells, the expression of CRABP1 does not affect the studied characteristics.Conclusion. CRABP1 stimulates growth and suppresses the RA-sensitivity of HER2(+) RA-sensitive cells, but does not have a similar effect on highly aggressive triple-negative RA-resistant cells.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. Π Π΅ΡΠΈΠ½ΠΎΠ΅Π²Π°Ρ ΠΊΠΈΡΠ»ΠΎΡΠ° (Π Π) Π·Π° ΡΡΠ΅Ρ ΠΌΠΎΠ΄ΡΠ»ΡΡΠΈΠΈ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΈ ΡΡΠ΄Π° ΡΠ΅ΡΠΈΠ½ΠΎΠΈΠ΄ΡΠ΅ΡΠΏΠΎΠ½ΡΠΈΠ²Π½ΡΡ
Π³Π΅Π½ΠΎΠ² ΡΡΠ°ΡΡΠ²ΡΠ΅Ρ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΠΏΡΠΎΡΠ΅ΡΡΠΎΠ² Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΡΠΎΠ²ΠΊΠΈ ΠΈ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠΈ. ΠΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΡ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ Π±Π΅Π»ΠΊΠΎΠ²-ΡΠ°ΠΏΠ΅ΡΠΎΠ½ΠΎΠ², ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΡ
Π Π, CRABP1 ΠΈ CRABP2 (Cellular Retinoic Acid Proteins-1 ΠΈ -2), Π² ΡΠ΅Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π Π, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΈΡ
ΡΡΠ°ΡΡΠΈΠ΅ Π² ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠΉ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΠΈ Π΄ΠΎ ΡΠΈΡ
ΠΏΠΎΡ ΠΏΠΎΠ»Π½ΠΎΡΡΡΡ Π½Π΅ΡΡΠ½Ρ. ΠΠΎΡΠ»Π΅Π΄Π½ΠΈΠ΅ Π΄Π°Π½Π½ΡΠ΅ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡ ΠΎ ΡΠΎΠΌ, ΡΡΠΎ ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΠ΅ ΡΠ°Π·Π»ΠΈΡΠΈΡ ΠΌΠ΅ΠΆΠ΄Ρ Π±Π΅Π»ΠΊΠ°ΠΌΠΈ CRABP Π² ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠΈ ΠΌΠ°Π»ΠΈΠ³Π½ΠΈΠ·Π°ΡΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ (Π ΠΠ) ΠΌΠΎΠ³ΡΡ Π±ΡΡΡ ΡΠ²ΡΠ·Π°Π½Ρ Ρ ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡΡ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ ΠΊ Π Π ΠΈ Ρ ΡΠ°Π·Π½ΡΠΌ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΠΌ ΡΡΠ°ΡΡΡΠΎΠΌ ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΠΎΠ΄ΠΈΡΡΡΡΡΡ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡ CRABP1 Π³ΠΈΠΏΠ΅ΡΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π»ΠΈ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ
Π ΠΠ Ρ ΠΎΡΡΡΡΡΡΠ²ΠΈΠ΅ΠΌ ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΠΎΠΉ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π΄Π°Π½Π½ΠΎΠ³ΠΎ Π±Π΅Π»ΠΊΠ°, ΡΠ°Π·Π½ΡΠΌ ΡΡΠΎΠ²Π½Π΅ΠΌ Π Π-ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΠΌ ΡΡΠ°ΡΡΡΠΎΠΌ β Π»ΠΈΠ½ΠΈΠΈ SKBR3 (Π Π-ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΡΠ΅, ER(β) / HER2(+)) ΠΈ MDA-MB-231 (Π Π-ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΡΠ΅, ΡΡΠΈΠΆΠ΄Ρ Π½Π΅Π³Π°ΡΠΈΠ²Π½ΡΠΉ ΡΡΠ°ΡΡΡ). ΠΡΠ΅Π½ΠΈΠ²Π°Π»ΠΈ ΡΠΎΡΡ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΡΡ
CRABP1(+)- ΠΈ ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½ΡΡ
ΡΡΠ±Π»ΠΈΠ½ΠΈΠΉ ΠΊΠ»Π΅ΡΠΎΠΊ Π² ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΡΡ
ΡΡΠ»ΠΎΠ²ΠΈΡΡ
ΠΊΡΠ»ΡΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈ Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΉ Π Π.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΎ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ CRABP1 Π² ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΡΡ
ΠΈ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΡΡ
ΠΊ Π Π ΠΊΠ»Π΅ΡΠΊΠ°Ρ
Π ΠΠ Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠΌ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΠΌ ΡΡΠ°ΡΡΡΠΎΠΌ Π½Π° Π΄ΠΈΠ½Π°ΠΌΠΈΠΊΡ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠΈ ΠΈ ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΊ Π Π. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ CRABP1 Π² ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΡΡ
ΠΊ Π Π ΠΊΠ»Π΅ΡΠΊΠ°Ρ
SKBR3 ΡΡΠΈΠΌΡΠ»ΠΈΡΡΠ΅Ρ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ Π² ΠΎΡΡΡΡΡΡΠ²ΠΈΠ΅ Π Π ΠΈ ΡΠ½ΠΈΠΆΠ°Π΅Ρ Π°Π½ΡΠΈΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠ²Π½ΡΠΉ ΡΡΡΠ΅ΠΊΡ Π Π, Π² ΡΠΎ Π²ΡΠ΅ΠΌΡ ΠΊΠ°ΠΊ Π² ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΡΡ
ΠΊΠ»Π΅ΡΠΊΠ°Ρ
MDA-MB-231 ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ CRABP1 Π½Π΅ Π²Π»ΠΈΡΠ΅Ρ Π½Π° ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΡΠ΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. CRABP1 ΡΡΠΈΠΌΡΠ»ΠΈΡΡΠ΅Ρ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠ²Π½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΈ ΡΠ½ΠΈΠΆΠ°Π΅Ρ ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΠΊ Π Π HER2(+)-ΠΊΠ»Π΅ΡΠΎΠΊ Π ΠΠ, Π½ΠΎ Π½Π΅ ΠΎΠΊΠ°Π·ΡΠ²Π°Π΅Ρ Π°Π½Π°Π»ΠΎΠ³ΠΈΡΠ½ΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ Π½Π° Π²ΡΡΠΎΠΊΠΎΠ°Π³ΡΠ΅ΡΡΠΈΠ²Π½ΡΠ΅ ΡΡΠΈΠΆΠ΄Ρ Π½Π΅Π³Π°ΡΠΈΠ²Π½ΡΠ΅ ΠΊΠ»Π΅ΡΠΊΠΈ, ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΡΠ΅ ΠΊ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ Π Π
Π Π΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ ΠΊ ΠΏΠΎΠ»Π½ΠΎΡΡΡΡ ΡΡΠ°Π½ΡΡΠ΅ΡΠΈΠ½ΠΎΠ΅Π²ΠΎΠΉ ΠΊΠΈΡΠ»ΠΎΡΠ΅ Π°ΡΡΠΎΡΠΈΠΈΡΠΎΠ²Π°Π½Π° ΡΠΎ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ΠΌ Π±Π°Π·Π°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΡΠΎΠ²Π½Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΡΠ΄Π΅ΡΠ½ΠΎΠ³ΠΎ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° RARΞ± ΠΈ ΠΈΠ½Π΄ΡΠΊΡΠΈΠΈ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΡΠΈΡΠΎΡ ΡΠΎΠΌΠΎΠ² CYP26A1 ΠΈ CYP26Π1
Introduction. Retinoic acid (RA) is a key regulator of cell differentiation and a critical player in such systemic processes in the body as embryonic development, immune system cell maturation and functioning, tissue remodeling and several others. This compound displays an antitumor activity due to its ability to stimulate differentiation, induce apoptosisΒ and inhibit proliferation of malignant cells. The rapid acquisition of resistance to RA and its analogues by solid tumor cells is one of the main problems limiting the widespread use of retinoids in the therapy of malignant neoplasms. The mechanisms of RA-resistance are still poorly understood.The study objective β assessment of the relationship between the basal expression level of the nuclear RARΞ± receptor and the RA-induced expression of the cytochromes CYP26A1and CYP26B1 with the resistance of breast cancer cells to the action of all-trans-retinoic acid.Materials and methods. Cell lines were cultured, the sensitivity of breast cancer cells to the action of fully trans-retinoic acid, RNA isolation, reverse transcription reaction and real-time polymerase chain reaction were analyzed).Results. In present study, using an experimental model represented by 9 breast cancer cell lines with different level of sensitivity to RA, we showed that the expression of the RA nuclear receptor RARΞ±, as well as the level of mRNA induction of CYP26A1 and CYP26B1 cytochromes in response to RA treatment correlate with RA-sensitivity.Conclusion. Thus, a decrease of RARΞ± expression as well as the reduced ability to catabolize RA are factors associated with RA-resistance of breast cancer cells.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. Π Π΅ΡΠΈΠ½ΠΎΠ΅Π²Π°Ρ ΠΊΠΈΡΠ»ΠΎΡΠ° (Π Π) ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΎΠ΄Π½ΠΈΠΌ ΠΈΠ· ΠΊΠ»ΡΡΠ΅Π²ΡΡ
ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠΎΠ² Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΡΠΎΠ²ΠΊΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΈ Π²Π°ΠΆΠ½Π΅ΠΉΡΠΈΠΌ ΡΡΠ°ΡΡΠ½ΠΈΠΊΠΎΠΌ ΡΠ°ΠΊΠΈΡ
ΡΠΈΡΡΠ΅ΠΌΠ½ΡΡ
ΠΏΡΠΎΡΠ΅ΡΡΠΎΠ² Π² ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ΅, ΠΊΠ°ΠΊ ΡΠΌΠ±ΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΠ΅ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅, ΡΠΎΠ·ΡΠ΅Π²Π°Π½ΠΈΠ΅ ΠΈ ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΈΠΌΠΌΡΠ½Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ, ΡΠ΅ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΊΠ°Π½Π΅ΠΉ ΠΈ ΡΡΠ΄ Π΄ΡΡΠ³ΠΈΡ
. ΠΡΠΎ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅ ΠΎΠ±Π»Π°Π΄Π°Π΅Ρ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΡ Π±Π»Π°Π³ΠΎΠ΄Π°ΡΡ ΡΠ²ΠΎΠ΅ΠΉ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΡΡΠΈΠΌΡΠ»ΠΈΡΠΎΠ²Π°ΡΡ Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΡΠΎΠ²ΠΊΡ, ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°ΡΡ Π°ΠΏΠΎΠΏΡΠΎΠ· ΠΈ ΠΏΠΎΠ΄Π°Π²Π»ΡΡΡ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
Π½ΠΎΠ²ΠΎΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠΉ. ΠΡΡΡΡΠΎΠ΅ ΠΏΡΠΈΠΎΠ±ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΠΈ ΠΊ Π Π ΠΈ Π΅Π΅ Π°Π½Π°Π»ΠΎΠ³Π°ΠΌ ΠΊΠ»Π΅ΡΠΊΠ°ΠΌΠΈ ΡΠΎΠ»ΠΈΠ΄Π½ΡΡ
ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΠΉ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΎΠ΄Π½ΠΎΠΉ ΠΈΠ· ΠΎΡΠ½ΠΎΠ²Π½ΡΡ
ΠΏΡΠΎΠ±Π»Π΅ΠΌ, ΠΎΠ³ΡΠ°Π½ΠΈΡΠΈΠ²Π°ΡΡΠΈΡ
ΡΠΈΡΠΎΠΊΠΎΠ΅ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ Π΅ΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
ΠΈ ΡΠΈΠ½ΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ΅ΡΠΈΠ½ΠΎΠΈΠ΄ΠΎΠ² Π² ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
Π½ΠΎΠ²ΠΎΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠΉ. ΠΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΡ ΡΠ°Π·Π²ΠΈΡΠΈΡ Π΄Π°Π½Π½ΠΎΠΉ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΠΈ ΠΎΡΡΠ°ΡΡΡΡ Π΄ΠΎ ΡΠΈΡ
ΠΏΠΎΡ ΠΌΠ°Π»ΠΎΠΏΠΎΠ½ΡΡΠ½ΡΠΌΠΈ.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΠΎΡΠ΅Π½ΠΊΠ° ΡΠ²ΡΠ·ΠΈ ΡΡΠΎΠ²Π½Ρ Π±Π°Π·Π°Π»ΡΠ½ΠΎΠΉ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΡΠ΄Π΅ΡΠ½ΠΎΠ³ΠΎ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° RARΞ± ΠΈ Π Π-ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΡΠΈΡΠΎΡ
ΡΠΎΠΌΠΎΠ² CYP26A1 ΠΈ CYP26B1 Ρ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ ΠΊ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΏΠΎΠ»Π½ΠΎΡΡΡΡ ΡΡΠ°Π½ΡΡΠ΅ΡΠΈΠ½ΠΎΠ΅Π²ΠΎΠΉ ΠΊΠΈΡΠ»ΠΎΡΡ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΡΠΎΠ²Π΅Π΄Π΅Π½Ρ ΠΊΡΠ»ΡΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
Π»ΠΈΠ½ΠΈΠΉ, Π°Π½Π°Π»ΠΈΠ· ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ ΠΊ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΏΠΎΠ»Π½ΠΎΡΡΡΡ ΡΡΠ°Π½ΡΡΠ΅ΡΠΈΠ½ΠΎΠ΅Π²ΠΎΠΉ ΠΊΠΈΡΠ»ΠΎΡΡ, Π²ΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ Π ΠΠ, ΠΎΠ±ΡΠ°ΡΠ½Π°Ρ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΡ ΠΈ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ°Π·Π½Π°Ρ ΡΠ΅ΠΏΠ½Π°Ρ ΡΠ΅Π°ΠΊΡΠΈΡ Π² ΡΠ΅Π°Π»ΡΠ½ΠΎΠΌ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΒ Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΠ΅ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΠΎΠΉ ΠΌΠΎΠ΄Π΅Π»ΠΈ, Π²ΠΊΠ»ΡΡΠ°ΡΡΠ΅ΠΉ 9 Π»ΠΈΠ½ΠΈΠΉ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ, ΡΠ°Π·Π»ΠΈΡΠ°ΡΡΠΈΡ
ΡΡ ΠΏΠΎ ΡΡΠΎΠ²Π½Ρ ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΊ Π Π, ΠΌΡ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ, ΡΡΠΎ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΠΌΠ°ΡΡΠΈΡΠ½ΠΎΠΉ Π ΠΠ Π³Π΅Π½Π° ΡΠ΄Π΅ΡΠ½ΠΎΠ³ΠΎ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° Π Π, RARΞ±, Π° ΡΠ°ΠΊΠΆΠ΅ ΡΡΠΎΠ²Π΅Π½Ρ ΠΈΠ½Π΄ΡΠΊΡΠΈΠΈ ΠΌΠ°ΡΡΠΈΡΠ½ΠΎΠΉ Π ΠΠ Π³Π΅Π½ΠΎΠ² ΡΠΈΡΠΎΡ
ΡΠΎΠΌΠΎΠ² CYP26A1 ΠΈ CYP26Π1 Π² ΠΎΡΠ²Π΅Ρ Π½Π° ΠΎΠ±ΡΠ°Π±ΠΎΡΠΊΡ Π Π ΠΊΠΎΡΡΠ΅Π»ΠΈΡΡΡΡ Ρ Π Π-ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. Π’Π°ΠΊΠΈΠΌ ΠΎΠ±ΡΠ°Π·ΠΎΠΌ, ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ RARΞ± ΠΈ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΠΊΠ°ΡΠ°Π±ΠΎΠ»ΠΈΠ·ΠΈΡΠΎΠ²Π°ΡΡ Π Π ΡΠ²Π»ΡΡΡΡΡ ΡΠ°ΠΊΡΠΎΡΠ°ΠΌΠΈ, Π°ΡΡΠΎΡΠΈΠΈΡΠΎΠ²Π°Π½Π½ΡΠΌΠΈ Ρ Π Π-ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ
ΠΠ»ΠΈΡΠ½ΠΈΠ΅ Π½ΠΎΠΊΠ΄Π°ΡΠ½Π° ΠΊΠ°Π²Π΅ΠΎΠ»ΠΈΠ½Π°-1 Π½Π° Π±Π΅Π»ΠΊΠΎΠ²ΡΠΉ ΡΠΎΡΡΠ°Π² ΡΠΊΡΡΡΠ°ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ Π²Π΅Π·ΠΈΠΊΡΠ», ΡΠ΅ΠΊΡΠ΅ΡΠΈΡΡΠ΅ΠΌΡΡ ΠΊΠ»Π΅ΡΠΊΠ°ΠΌΠΈ Π½Π΅ΠΌΠ΅Π»ΠΊΠΎΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ°ΠΊΠ° Π»Π΅Π³ΠΊΠΈΡ
Background. Recent data show evidence that lipid rafts (LR) proteins could be involved in the formation of exosomes and the sorting of proteins that make up the exosomal cargo. Such data are available for flotillins, structural and functional components of flatted rafts. The presence of the main component of caveolar rafts, caveolin-1 (Cav-1), has been shown in exosomes produced by some cancer cells; however, its possible participation in the regulation of the protein composition of exosomes has not been studied previously.Materials and methods. Knockdown of Cav-1 by transduction of a lentiviral vector expressing precursors of short hairpin ribonucleic acid to Cav-1; isolation (by ultracentrifugation) and analysis (transmission electron microscopy, nanoparticle tracking analysis) of extracellular vesicles (EVs) from non-small cell lung cancer cells (NSCLC) H1299; analysis of proteins in cells and in EVs by immunoblotting.Results. Analysis of the effect of Cav-1 expression on the composition of EV proteins associated with exosome biogenesis revealed a decrease in the level of Alix and TSG101, an increase in the level of LR proteins and the absence of changes in the level of tetraspanin CD9.Β Conclusion. The obtained data demonstrate a Cav-1-dependent changes in the composition of EVs, indicating aΒ change in the ratio of vesicles formed by the various molecular mechanisms.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. ΠΠ°Π½Π½ΡΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΡ
Π»Π΅Ρ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡ ΠΎΒ ΡΠΎΠΌ, ΡΡΠΎΒ Π±Π΅Π»ΠΊΠΈ, Π²Ρ
ΠΎΠ΄ΡΡΠΈΠ΅ Π²Β ΡΠΎΡΡΠ°Π² Π»ΠΈΠΏΠΈΠ΄Π½ΡΡ
ΡΠ°ΡΡΠΎΠ², ΠΌΠΎΠ³ΡΡ Π±ΡΡΡ Π·Π°Π΄Π΅ΠΉΡΡΠ²ΠΎΠ²Π°Π½Ρ Π²Β ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΡΠΊΠ·ΠΎΡΠΎΠΌ ΠΈΒ ΠΎΡΠ±ΠΎΡΠ΅ Π±Π΅Π»ΠΊΠΎΠ², Π²Ρ
ΠΎΠ΄ΡΡΠΈΡ
Π²Β ΡΠΎΡΡΠ°Π² ΡΠΊΠ·ΠΎΡΠΎΠΌΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΊΠ°ΡΠ³ΠΎ. Π’Π°ΠΊΠΈΠ΅ Π΄Π°Π½Π½ΡΠ΅ ΠΏΠΎΠ»ΡΡΠ΅Π½Ρ Π΄Π»ΡΒ ΡΠ»ΠΎΡΠΈΠ»Π»ΠΈΠ½ΠΎΠ², ΡΡΡΡΠΊΡΡΡΠ½ΠΎ-ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΡ
ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠΎΠ² ΠΏΠ»ΠΎΡΠΊΠΈΡ
ΡΠ°ΡΡΠΎΠ². ΠΠ»ΡΒ ΠΊΠ°Π²Π΅ΠΎΠ»ΠΈΠ½Π°-1 (Cav-1), ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠ° ΠΊΠ°Π²Π΅ΠΎΠ»ΡΡΠ½ΡΡ
ΡΠ°ΡΡΠΎΠ², ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠ΅ Π²Β ΡΠΊΠ·ΠΎΡΠΎΠΌΠ°Ρ
Π½Π΅ΠΊΠΎΡΠΎΡΡΡ
ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ, ΠΎΠ΄Π½Π°ΠΊΠΎ Π΅Π³ΠΎ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠ΅ ΡΡΠ°ΡΡΠΈΠ΅ Π²Β ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ Π±Π΅Π»ΠΊΠΎΠ²ΠΎΠ³ΠΎ ΡΠΎΡΡΠ°Π²Π° ΡΠΊΠ·ΠΎΡΠΎΠΌ ΡΠ°Π½Π΅Π΅ Π½Π΅Β ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π»ΠΎΡΡ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈΒ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΠΎΠΊΠ΄Π°ΡΠ½ Cav-1 ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΡΡΠ°Π½ΡΠ΄ΡΠΊΡΠΈΠΈ Π»Π΅Π½ΡΠΈΠ²ΠΈΡΡΡΠ½ΠΎΠ³ΠΎ Π²Π΅ΠΊΡΠΎΡΠ°, ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡΡΡΡΠ΅Π³ΠΎ ΠΏΡΠ΅Π΄ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΈΠΊΠΎΠ² ΠΌΠ°Π»ΡΡ
ΡΠΏΠΈΠ»Π΅ΡΠ½ΡΡ
ΡΠΈΠ±ΠΎΠ½ΡΠΊΠ»Π΅ΠΈΠ½ΠΎΠ²ΡΡ
ΠΊΠΈΡΠ»ΠΎΡ ΠΊΒ Cav-1. ΠΠΊΡΡΡΠ°ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠ΅ Π²Π΅Π·ΠΈΠΊΡΠ»Ρ (ΠΠΠ) Π²ΡΠ΄Π΅Π»ΡΠ»ΠΈ ΠΈΠ·Β ΠΊΠ»Π΅ΡΠΎΠΊ Π»ΠΈΠ½ΠΈΠΈ Π1299 Π½Π΅ΠΌΠ΅Π»ΠΊΠΎΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ°ΠΊΠ° Π»Π΅Π³ΠΊΠΈΡ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ»ΡΡΡΠ°ΡΠ΅Π½ΡΡΠΈΡΡΠ³ΠΈΡΠΎΠ²Π°Π½ΠΈΡ. ΠΡΠ΅ΠΏΠ°ΡΠ°ΡΡ ΠΠΠ Π²Π΅ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π»ΠΈ ΡΒ ΠΏΠΎΠΌΠΎΡΡΡ ΡΡΠ°Π½ΡΠΌΠΈΡΡΠΈΠΎΠ½Π½ΠΎΠΉ ΡΠ»Π΅ΠΊΡΡΠΎΠ½Π½ΠΎΠΉ ΠΌΠΈΠΊΡΠΎΡΠΊΠΎΠΏΠΈΠΈ (Π°Π½Π°Π»ΠΈΠ· ΡΠ°Π·ΠΌΠ΅ΡΠ° ΠΈΒ ΠΌΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΠΈ) ΠΈΒ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Π°Π½Π°Π»ΠΈΠ·Π° ΡΡΠ°Π΅ΠΊΡΠΎΡΠΈΠΉ Π΄Π²ΠΈΠΆΠ΅Π½ΠΈΡ Π½Π°Π½ΠΎΡΠ°ΡΡΠΈΡ (ΡΡΠ΅Π΄Π½Π΅ΡΠ°Π·ΠΌΠ΅ΡΠ½ΠΎΠ΅ ΡΠ°ΡΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΈΒ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡ). ΠΠ»ΡΒ Π°Π½Π°Π»ΠΈΠ·Π° ΡΠΊΠ·ΠΎΡΠΎΠΌΠ°Π»ΡΠ½ΡΡ
ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² ΠΈΒ Cav-1 Π²Β ΠΊΠ»Π΅ΡΠΊΠ°Ρ
ΠΈΒ ΠΠΠ ΠΏΡΠΈΠΌΠ΅Π½ΡΠ»ΠΈ ΠΌΠ΅ΡΠΎΠ΄ ΠΈΠΌΠΌΡΠ½ΠΎΠ±Π»ΠΎΡΡΠΈΠ½Π³Π°.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΠ½Π°Π»ΠΈΠ· Π²Π»ΠΈΡΠ½ΠΈΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Cav-1 Π½Π°Β ΡΠΎΡΡΠ°Π² Π±Π΅Π»ΠΊΠΎΠ² ΠΠΠ, Π°ΡΡΠΎΡΠΈΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΡΒ Π±ΠΈΠΎΠ³Π΅Π½Π΅Π·ΠΎΠΌ ΡΠΊΠ·ΠΎΡΠΎΠΌ, Π²ΡΡΠ²ΠΈΠ» ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ ΡΡΠΎΠ²Π½Ρ Alix ΠΈΒ TSG101, ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅ ΡΡΠΎΠ²Π½Ρ Π±Π΅Π»ΠΊΠΎΠ² Π»ΠΈΠΏΠΈΠ΄Π½ΡΡ
ΡΠ°ΡΡΠΎΠ² ΠΈΒ ΠΎΡΡΡΡΡΡΠ²ΠΈΠ΅ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ ΡΡΠΎΠ²Π½Ρ ΡΠ΅ΡΡΠ°ΡΠΏΠ°Π½ΠΈΠ½Π° CD9.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ Π΄Π°Π½Π½ΡΠ΅ Π΄Π΅ΠΌΠΎΠ½ΡΡΡΠΈΡΡΡΡ Cav-1-Π·Π°Π²ΠΈΡΠΈΠΌΠΎΠ΅ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΡΠΎΡΡΠ°Π²Π° ΠΠΠ, ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡΠ΅Π΅ ΠΎΠ± ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΈ ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΡ Π²Π΅Π·ΠΈΠΊΡΠ», ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½Π½ΡΡ
Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΡ
ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠ².
ΠΠ΅ΠΊΠ°Π½ΠΎΠ½ΠΈΡΠ΅ΡΠΊΠ°Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠ΅ΡΠΈΠ½ΠΎΠ΅Π²ΠΎΠΉ ΠΊΠΈΡΠ»ΠΎΡΡ Π² ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠΈ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠΈ ΠΏΡΠΎΡΠ΅ΠΈΠ½ΠΊΠΈΠ½Π°Π· Π² ΡΡΠ°Π½ΡΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½Π½ΡΡ ΠΊΠ»Π΅ΡΠΊΠ°Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΠΎΠ³ΠΎ ΠΏΡΠΎΠΈΡΡ ΠΎΠΆΠ΄Π΅Π½ΠΈΡ
Background. The non-canonical activity of retinoic acid (RA) was discovered relatively recently and consists in the rapid activation of intracellular signaling pathways by the mechanisms not related to the transcriptional activity of the RA nuclear receptors. Separate data suggest that this activity can stimulate the processes of malignancy and contribute to the formation of tumor cell resistance to RA as a therapeutic agent. However, little is known about the mechanisms of this activity. It is also unclear how universal this effect is; does the RA-dependent activation of different signaling protein kinases occur in the same cells, and whether activation of these kinases is interrelated.Materials and methods: cultivation of non-small cell lung cancer cells and neuroblastoma cells under standard conditions and with incubation with all-trans retinoic acid (ATRA); immunoblotting.Results. Here we studied the effect of ATRA on the activation of Akt and Erk1/2 protein kinases depending on the incubation time. The analysis revealed RA-dependent activation of both kinases in all studied non-small cell lung cancer and neuroblastoma cell lines. Activation of Akt and Erk1/2 occurred at five minutes of incubation, which corresponds to the non-transcriptional (non-canonical) activity of the RA, however, further activation kinetics of the two kinases differed essentially.Conclusion. We found that ATRA causes rapid activation of Erk1/2 and Akt protein kinases in both non-small cell lung cancer and neuroblastoma cells. The differences in the kinetics of RA-dependent stimulation of these two kinases suggest that their activation is mediated by independent mechanisms.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. ΠΠ΅ΠΊΠ°Π½ΠΎΠ½ΠΈΡΠ΅ΡΠΊΠ°Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠ΅ΡΠΈΠ½ΠΎΠ΅Π²ΠΎΠΉ ΠΊΠΈΡΠ»ΠΎΡΡ (Π Π) ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½Π° ΡΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΠΎ Π½Π΅Π΄Π°Π²Π½ΠΎ ΠΈ Π·Π°ΠΊΠ»ΡΡΠ°Π΅ΡΡΡ Π² Π±ΡΡΡΡΠΎΠΉ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠΈ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΡ
ΠΏΡΡΠ΅ΠΉ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠ², Π½Π΅ ΡΠ²ΡΠ·Π°Π½Π½ΡΡ
Ρ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΎΠ½Π½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΡ ΡΠ΄Π΅ΡΠ½ΡΡ
ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² Π Π. ΠΡΠ΄Π΅Π»ΡΠ½ΡΠ΅ Π΄Π°Π½Π½ΡΠ΅ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡ ΠΎ ΡΠΎΠΌ, ΡΡΠΎ Π½Π΅ΠΊΠ°Π½ΠΎΠ½ΠΈΡΠ΅ΡΠΊΠ°Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΌΠΎΠΆΠ΅Ρ ΡΡΠΈΠΌΡΠ»ΠΈΡΠΎΠ²Π°ΡΡ ΠΏΡΠΎΡΠ΅ΡΡΡ ΠΌΠ°Π»ΠΈΠ³Π½ΠΈΠ·Π°ΡΠΈΠΈ ΠΈ ΡΡΠ°ΡΡΠ²ΠΎΠ²Π°ΡΡ Π² ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΠΈ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ ΠΊ ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΎΠΌΡ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΡ Π Π. ΠΠ΄Π½Π°ΠΊΠΎ ΠΎ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠ°Ρ
Π½Π΅ΠΊΠ°Π½ΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈΠ·Π²Π΅ΡΡΠ½ΠΎ Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎ ΠΌΠ°Π»ΠΎ. ΠΠ΅ΠΏΠΎΠ½ΡΡΠ½ΠΎ, Π½Π°ΡΠΊΠΎΠ»ΡΠΊΠΎ ΡΡΠΎΡ ΡΡΡΠ΅ΠΊΡ ΡΠ½ΠΈΠ²Π΅ΡΡΠ°Π»Π΅Π½, ΠΏΡΠΎΠΈΡΡ
ΠΎΠ΄ΠΈΡ Π»ΠΈ Π Π-Π·Π°Π²ΠΈΡΠΈΠΌΠ°Ρ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΡ
ΠΏΡΠΎΡΠ΅ΠΈΠ½ΠΊΠΈΠ½Π°Π· Π² ΠΎΠ΄Π½ΠΈΡ
ΠΈ ΡΠ΅Ρ
ΠΆΠ΅ ΠΊΠ»Π΅ΡΠΊΠ°Ρ
, ΠΈ Π½Π°ΡΠΊΠΎΠ»ΡΠΊΠΎ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ ΡΡΠΈΡ
ΠΊΠΈΠ½Π°Π· Π²Π·Π°ΠΈΠΌΠΎΡΠ²ΡΠ·Π°Π½Π°.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ: ΠΊΡΠ»ΡΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΊΠ»Π΅ΡΠΎΠΊ Π½Π΅ΠΌΠ΅Π»ΠΊΠΎΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ°ΠΊΠ° Π»Π΅Π³ΠΊΠΎΠ³ΠΎ ΠΈ Π½Π΅ΠΉΡΠΎΠ±Π»Π°ΡΡΠΎΠΌΡ Π² ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΡΡ
ΡΡΠ»ΠΎΠ²ΠΈΡΡ
ΠΈ ΠΏΡΠΈ ΠΈΠ½ΠΊΡΠ±Π°ΡΠΈΠΈ Ρ ΠΏΠΎΠ»Π½ΠΎΡΡΡΡ ΡΡΠ°Π½Ρ-ΡΠ΅ΡΠΈΠ½ΠΎΠ΅Π²ΠΎΠΉ ΠΊΠΈΡΠ»ΠΎΡΠΎΠΉ (all-trans retinoic acid, ATRA); ΠΈΠΌΠΌΡΠ½ΠΎΠ±Π»ΠΎΡΡΠΈΠ½Π³.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. Π ΡΠ°Π±ΠΎΡΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π»ΠΈ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ATRA Π½Π° Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ ΠΏΡΠΎΡΠ΅ΠΈΠ½ΠΊΠΈΠ½Π°Π· Akt ΠΈ Erk1 / 2 Π² Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ ΠΈΠ½ΠΊΡΠ±Π°ΡΠΈΠΈ. ΠΠ½Π°Π»ΠΈΠ· Π²ΡΡΠ²ΠΈΠ» Π Π-Π·Π°Π²ΠΈΡΠΈΠΌΡΡ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ ΠΎΠ±Π΅ΠΈΡ
ΠΊΠΈΠ½Π°Π· Π²ΠΎ Π²ΡΠ΅Ρ
ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΡΡ
Π»ΠΈΠ½ΠΈΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ Π½Π΅ΠΌΠ΅Π»ΠΊΠΎΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ°ΠΊΠ° Π»Π΅Π³ΠΊΠΎΠ³ΠΎ ΠΈ Π½Π΅ΠΉΡΠΎΠ±Π»Π°ΡΡΠΎΠΌΡ. ΠΠΊΡΠΈΠ²Π°ΡΠΈΡ ΠΊΠ°ΠΊ Akt, ΡΠ°ΠΊ ΠΈ Erk1 / 2 Π²ΠΎΠ·Π½ΠΈΠΊΠ°Π»Π° ΠΏΡΠΈ 5 ΠΌΠΈΠ½ ΠΈΠ½ΠΊΡΠ±Π°ΡΠΈΠΈ, ΡΡΠΎ ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΡΠ΅Ρ Π½Π΅ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΎΠ½Π½ΠΎΠΉ (Π½Π΅ΠΊΠ°Π½ΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ) Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π Π, ΠΎΠ΄Π½Π°ΠΊΠΎ Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠ°Ρ ΠΊΠΈΠ½Π΅ΡΠΈΠΊΠ° Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠΈ Π΄Π²ΡΡ
ΠΊΠΈΠ½Π°Π· ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎ ΡΠ°Π·Π»ΠΈΡΠ°Π»Π°ΡΡ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΡ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ, ΡΡΠΎ ATRA Π²ΡΠ·ΡΠ²Π°Π΅Ρ ΠΊΡΠ°ΡΠΊΠΎΡΡΠΎΡΠ½ΡΡ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ ΠΏΡΠΎΡΠ΅ΠΈΠ½ΠΊΠΈΠ½Π°Π· Erk1 / 2 ΠΈ Akt Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ
Π½Π΅ΠΌΠ΅Π»ΠΊΠΎΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ°ΠΊΠ° Π»Π΅Π³ΠΊΠΎΠ³ΠΎ ΠΈ Π½Π΅ΠΉΡΠΎΠ±Π»Π°ΡΡΠΎΠΌΡ. Π Π°Π·Π»ΠΈΡΠΈΡ Π² ΠΊΠΈΠ½Π΅ΡΠΈΠΊΠ΅ Π Π-Π·Π°Π²ΠΈΡΠΈΠΌΠΎΠΉ ΡΡΠΈΠΌΡΠ»ΡΡΠΈΠΈ Π΄Π²ΡΡ
ΠΊΠΈΠ½Π°Π· ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡ ΠΎ ΡΠΎΠΌ, ΡΡΠΎ ΠΈΡ
Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ ΡΠ΅Π°Π»ΠΈΠ·ΡΠ΅ΡΡΡ Ρ ΠΏΠΎΠΌΠΎΡΡΡ Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΡΡ
ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠ²
Ability to form duplexes as a factor of intracellular microRNA distribution
Background. The regulation of the content of mature microRNAs (miRNAs) in different cell compartments β the nucleus (N) and the cytoplasm (C) β makes it possible to control their availability for participation in RNA-mediated interference processes. Structurally different miRNAs, processed from different precursors (pre-miRNA), can form duplexes between molecules containing complementary sequences. The appearance of such duplexes can be considered as one of the mechanisms of miRNA activity regulation in respect to their target mRNAs. Objectives. Analysis of the miRNA distribution between nucleus and cytoplasm depending on the energy of duplex formation. Materials and methods. Data on the content of different miRNAs in the nucleus and cytoplasm in two cell lines of different origin: 5-8F of human nasopharyngeal carcinoma (NPC) and postmitotic neurons of the cerebral cortex of rat β has been used. The miRNA sequences used for analysis were taken from the miRBase database, version 22. Bioinformatic analysis of miRNA sequences for detection of molecules capable of forming miRNA duplexes and determination of their minimal free energy (MFE) of formation was carried out with the help of programs: RegRNA, version 2.0, and RNAup.Β Results. For the first time, a comparative analysis of the intracellular distribution N/C of different miRNAs depending on the energy of duplex formation was performed. Results of bioinformatic analysis of miRNA sequencing in 5-8F cells of human nasopharyngeal carcinoma showed that miRNAs capable of forming high-energy, i. e. more stable, duplexes, accumulate in the cytoplasm, while miRNAs forming low-energy duplexes have a larger N/C value, i. e. the level of these miRNAs is higher in the nucleus. In addition, we show that N/C distribution of miRNAs capable of forming high-energy duplexes is independent from the presence of certain short motifs, that are supposedly associated with their nuclear localization. Conclusion. The revealed enrichment of the pool of cytoplasmic miRNAs by molecules capable of forming more energetically stable duplexes may represent an additional mechanism of regulating miRNA activity in respect to their target mRNAs due to the sequestration of miRNA duplexes in the cytoplasm preventing miRNA interaction with mRNAs