


Том 41, № 4 (2024)
ОБЗОРЫ
Expression of myoglobin by tumor cells and its role in progression of malignancy
Аннотация
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.



Mitochondrial donation as a mechanism of participation by mesenchymal stromal cells in regenerative processes
Аннотация
Mesenchymal stromal cells (MSCs) are universal regulators of regenerative processes due to their ability to secrete regulatory molecules or replace dead cells through differentiation in the appropriate direction. Recently, another mechanism for the beneficial effects of MSCs on damaged tissue has been discovered, such as the transfer of mitochondria into its cells in response to stress signals. MSCs can transfer mitochondria through tunneling nanotubes that form a communication bridge between cells, through gap junctions, by release as part of extracellular vesicles or in free form, and as a result of complete or partial fusion with recipient cells. In damaged cells that received mitochondria from MSCs, impaired energy metabolism is restored and oxidative stress is reduced, which is accompanied by increased survival, and in some cases also increased proliferation or a change in differentiation status. The restoration of energy after the transfer of mitochondria from MSCs has a beneficial effect on the functional activity of recipient cells and suppresses inflammatory reactions. A significant contribution of the MSC mitochondrial donation to the therapeutic efficacy of MSCs has been repeatedly demonstrated in models of damage to various organs in experimental animals. This stimulates the search for methods to enhance the process of mitochondrial donation. However, it should be taken into account that MSCs are able to transfer mitochondria to malignant cells as well, thereby stimulating tumor growth and increasing its resistance to chemotherapy. These data make it necessary to evaluate the prospects for the use of MSCs in cell therapy with caution. On the other hand, they can serve as a basis for the search for new therapeutic targets in the treatment of oncological diseases.



Articles
Cationic and ionizable amphiphiles based on di-hexadecyl ester of L-glutamic acid for liposomal transport of RNA
Аннотация
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.



Seasonal changes in the content of fatty acids in the skeletal muscles of the long-tailed ground squirrel Urocitellus undulatus
Аннотация
Seasonal changes in the fatty acid composition in four skeletal muscles of the true hibernant Yakut long-tailed ground squirrel Urocitellus undulatus were studied. Measurements were taken on animals of four experimental groups: summer active, autumn active, winter dormant, and winter active. An increase in the total amount of fatty acids was found in winter in the quadriceps muscle of the thigh (m. vastus lateralis), the triceps muscle of the forearm (m. triceps), and the psoas muscle (m. psoas). In all muscles, including m. gastrocnemius, a decrease in the total amount of saturated fatty acids was observed in winter. An increase in the total amount of monounsaturated fatty acids in winter hibernating animals occurred in the quadriceps femoris muscle, triceps muscle of the forearm, and in the psoas muscle. In winter active animals, the total content of polyunsaturated fatty acids in the quadriceps femoris and psoas muscles increased. A significant decrease in palmitic acid content in sleeping and winter active ground squirrels compared to summer and autumn animals was found in all muscles studied. The amount of palmitoleic acid significantly increased in sleeping animals in the quadriceps femoris and psoas muscles. In the triceps muscle of the forearm. the amount of palmitoleic acid increased in autumn active and winter dormant individuals. The amount of oleic acid was increased in all muscles of winter hibernating animals relative to active autumn animals. The content of linoleic acid significantly increased in winter active ground squirrels in all muscles except the gastrocnemius. In the autumn period the amount of dihomo-gamma-linolenic acid also increased in all muscles, with a significant decrease in its content in winter sleeping and winter active animals to the level of summer (seasonal) control. The results obtained indicate that most changes in fatty acid composition have the same direction in all four studied skeletal muscles of the long-tailed ground squirrel. Possible roles of seasonal changes in fatty acid composition and the participation of fatty acids in biochemical processes in the muscle tissue of the long-tailed ground squirrel are discussed.



Distribution of progesterone receptors and the membrane component of progesterone receptor in various organs and tissues of male and female rats
Аннотация
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.


