Vol 40, No 1 (2023)

A growing number of studies indicate the relationship between the development of neurodegenerative diseases and the structure and lipid composition of neuronal membranes. One of the structural elements of cell membranes, which in this regard attracts special attention, are liquid-ordered lipid domains, or rafts. The study of rafts and age-related changes in the lipid composition of neuronal cells is becoming increasingly relevant and is constantly being updated. In this review, we tried to highlight the possible role of the lipid component of cell membranes, their structure, and physicochemical characteristics in the development of diseases associated with aging. The reviewed evidence supports the possible role of rafts in diseases, which lead to disruption of the functioning of neurons over a long period of time. There is reason to believe that the therapeutic effects of various molecules, such as lysolipids and gangliosides, are due to their physicochemical properties and are realized indirectly, through their influence on the organization of lipid domains in membranes. As the role of lipid domains and, in general, the mechanisms of interaction and mutual influence of lipid composition and disease development are more fully understood, this knowledge can be used to develop new therapeutic or preventive methods to combat diseases associated with aging.

Many agonists regulate cellular functions through surface receptors coupled by the phosphoinositide cascade to Са²⁺ mobilization. In unexcitable cells, the generation of Са²⁺ signals relies largely on Са²⁺ release from из Са²⁺ store localized in the endoplasmic reticulum (ER). In this system, IP₃ receptors (IP₃Rs), which are intracellular IP₃-gated Са²⁺- channels, mediate controllable Ca²⁺ release from Ca²⁺ store in response to cell stimulation. A variety of factors embarrass both the analysis of a specific role for IP₃Rs in cell physiology and detailing their regulatory mechanisms. Firstly, three genes encode IP₃Rs, while cells usually express two or even all of them. Moreover, different IP₃R isoforms are under control of distinct mechanisms. Yet, isoform-specific antagonists of IP₃Rs have not been identified yet. Cell lines that express a single isoform appear to be an effective cellular model for studying regulatory mechanisms, pharmacology, and physiological role of I-P₃R subtypes. Here we employed the CRISPR/Cas9 technology to inactivate genes of IP₃Rs in cells of the HEK-293 line, which express all three isoforms. Several monoclones of genetically modified HEK-293 were obtained, and those containing biallelic inactivation mutation in two IP₃R genes were identified. Finally, three monoclonal cell lines, each containing the only functional IP₃R isoform, were generated. These cellular models can be used to evaluate a role for IP₃R of a particular subtype in agonist-induced Ca²⁺ signaling as well as for the analysis of their regulatory mechanisms.

Currently, experimental oncology is developing approaches based on the development of targeted photosensitizers that can be delivered specifically to a tumor of a certain molecular profile. This work is devoted to the study of the generation of reactive oxygen species by photosensitizers of protein nature 4D5scFv-miniSOG and DARPin-miniSOG, specific to the oncomarker HER2. It was found that despite the presence of the same phototoxic module in their composition, these photosensitizers are characterized by different levels of ROS production, which may be explained by the different rate of receptor-mediated internalization of 4D5scFv-miniSOG and DARPin-miniSOG.

The effect of exogenous auxin on the fatty acid composition of total lipids in leaves and roots of spring wheat seedlings (Triticum aestivum L.) was studied. It has been established that the diversity of fatty acids in vegetative organs (leaf or root) depends not only on the concentration of auxin, but also on the nitric oxide donor (N₂, NO₃). It was noted that increasing the concentration of exogenous auxin increased microviscosity and decreased the permeability of the membranes of the vegetative organ in wheat, which was accompanied by a decrease in the double bond index. At the same time, there is an increase in the concentration of saturated fatty acids (palmitic and stearic), which are used as precursors for the formation of fatty acids with a very long chain (VLCFA). It was shown that exogenous auxin leads to an increase in the total content of VLCFAs in leaves with a deficiency (8.4%) and an excess of NO donors (12.3%). The introduction of exogenous auxin eliminates significant differences in the activity of desaturases in wheat roots at different levels of nitric oxide donors. It is suggested that the biosynthesis of docosadienoic acid (C_22:2) in leaves is one of the key stages in the formation of an adaptive response of cell membranes to abiotic stresses during plant ontogenesis. An increase in the level of NO promotes the movement of auxin from roots to shoots, which can serve as a regulator of the activity of elongases and desaturases during the synthesis of VLCFAs.