卷 41, 编号 4 (2024)

The review examines available literature data on the expression of myoglobin in various tumors and tumor cell lines of non-muscle nature, and the effect of hypoxia, reactive oxygen and nitrogen species, hormones, growth factors, gender and age on this process. The influence of tumor myoglobin on processes occurring in cells – oxidative stress, inhibition of mitochondrial respiration by nitric oxide and fatty acid metabolism is also analyzed, both in the case of intrinsic endogenous (ectopic) expression of small amounts (~1 µM) of myoglobin and overexpression of the protein (~150 µM) via the myoglobin gene embedded in the tumour cell genome. It is concluded that hypoxia-induced intrinsic expression of low concentrations of myoglobin, due to its ability to utilise reactive oxygen and nitrogen species that can damage tumour cells, ensures their better survival, promoting tumour progression and metastasis. Accordingly, this myoglobin expression is generally associated with a more aggressive tumour type and poor prognosis for the course and outcome of the disease, and may thus serve as a “marker” of an aggressive malignancy. In contrast, artificial overexpression of myoglobin can significantly inhibit tumour development and improve disease course by switching cancer cell metabolism from tumour-specific glycolysis to oxidative phosphorylation inherent in healthy tissue. Myoglobin overexpression may thus be an effective therapeutic tool in oncology.

Various RNAs are among the most promising and actively developed therapeutic agents for the treatment of tumors, infectious diseases and a number of other pathologies associated with the dysfunction of specific genes. Some nanocarriers are used for the effective delivery of RNAs to target cells, including liposomes based on cationic and/or ionizable amphiphiles. Cationic amphiphiles contain a protonated amino group and exist as salts in an aqueous environment. Ionizable amphiphiles are a new generation of cationic lipids that exhibit reduced toxicity and immunogenicity and undergo ionization only in the acidic environment of the cell. In this work we developed a scheme for the preparation and carried out the synthesis of new cationic and ionizable amphiphiles based on natural amino acids (L-glutamic acid, glycine, beta-alanine, and gamma-aminobutyric acid). Cationic and ionizable liposomes were formed based on the obtained compounds, mixed with natural lipids (phosphatidylcholine and cholesterol), and their physicochemical characteristics (particle size, zeta potential, and storage stability) were determined. Average diameter of particles stable for 5–7 days did not exceed 100 nm. Zeta potential of cationic and ionizable liposomes was about 30 and 1 mV, respectively. The liposomal particles were used to form complexes with RNA molecules. Such RNA complexes were characterized by atomic force microscopy and their applicability for nucleic acid transport was determined.

Progesterone regulates reproductive processes and affects many functions of various non-reproductive organs. Its effects in mammals and humans are mediated by nuclear (nPRs) and membrane progesterone receptors (mPRs). The action of progesterone through different types of receptors may differ significantly and has tissue specific features. The expression of known types and subtypes of progesterone receptors in the tissues of male and female rats has been studied fragmentarily. The purpose of our work was to study the expression of five mPRs genes, as well as the nPRs gene and the membrane component of the progesterone receptor PGRMC I in the reproductive organs and in 17 non-reproductive tissues of male and female rats using reverse transcription followed by real-time PCR. In this study, it was shown that a high level of nPRs gene expression in rats is found not only in reproductive organs of females (uterus, ovary, mammary glands), but also in seminal vesicles of males, in the brain and trachea of both sexes, in blood vessels, and in the pancreas of females. The highest level of expression of mPRs genes of all subtypes was found in the testes, while expression of the gene encoding nPRs was practically undetectable in them. Expression of genes encoding mPRs was also detected in the liver and spleen of male and female rats, while expression of the gene encoding nPRs was at background levels. Virtually no expression of nPRs, mPRs, and membrane component of progesterone receptor (PGRMC I) genes was detected in muscle, and its level was very low in the heart in animals of both sexes. We found sex-specific differentiation of nuclear and membrane receptor mRNA levels in rats in non-reproductive tissues, characterized by a predominance of nPRs transcripts and three subtypes of mPRs (α, β, δ) in females and two subtypes of mPRs (γ, ε) in males. Data on the presence of progesterone receptors in tissues not involved in reproduction confirm the effect of progesterone on these organs. High levels of mRNA for various progesterone receptors in the tissues of male rats, such as the pancreas, lungs, kidney, and trachea, indicate an important physiological role of progestins not only in females, but also in males, which is still poorly understood. The work also discusses the known functions of progesterone receptors in the tissues studied.