There is accumulating evidence that mitochondria and mitochondrial STAT3 are involved in the activation of mast cells. The mitochondria-targeted curcuminoids Mitocur-1 and Mitocur-3 have been suggested to reduce antigen-dependent mast cell activation by inhibiting mitochondrial STAT3. The aim of the current work was to investigate the mechanisms of action of these mitocurcuminoids on mast cells and mitochondrial functions. The pretreatment of rat basophilic leukemia cells RBL-2H3 with Mitocur-1 and Mitocur-3 decreased antigen-dependent degranulation but did not affect spontaneous degranulation. Both compounds caused mitochondrial fragmentation and increased mitochondrial ROS. Inhibition of Drp1 prevented mitochondrial fragmentation induced by Mitocur-3 but not by Mitocur-1. The antioxidant N-acetylcysteine inhibited mitochondrial fission induced by Mitocur-1 but not Mitocur-3. Mitochondrial fragmentation caused by Mitocur-3 but not Mitocur-1 was accompanied by activation of Drp1 and AMPK. These data suggest a distinct mechanism of action of mitocurcuminoids on the mitochondria of RBL-2H3 cells: Mitocur-3 stimulated AMPK and caused Drp1-dependent mitochondrial fragmentation, while Mitocur-1-induced mitochondrial fission was ROS-dependent. This difference may contribute to the higher toxicity of Mitocur-3 compared to Mitocur-1. The findings contribute to further drug development for inflammatory and allergic diseases.

The significant role of mast cells in the development of allergic and inflammatory diseases is well-established. Among the various mechanisms of mast cell activation, the interaction of antigens/allergens with IgE and the subsequent binding of this complex to the high-affinity IgE receptor FcεRI stand out as the most studied and fundamental pathways. This activation process leads to the rapid exocytosis of granules containing preformed mediators, followed by the production of newly synthesized mediators, including a diverse array of cytokines, chemokines, arachidonic acid metabolites, and more. While conventional approaches to allergy control primarily focus on allergen avoidance and the use of antihistamines (despite their associated side effects), there is increasing interest in exploring novel methods to modulate mast cell activity in modern medicine. Recent evidence suggests a role for autophagy in mast cell activation, offering potential avenues for utilizing low-molecular-weight autophagy regulators in the treatment of allergic diseases. More specifically, mitochondria, which play an important role in the regulation of autophagy as well as mast cell activation, emerge as promising targets for drug development. This review examines the existing literature regarding the involvement of the molecular machinery associated with autophagy in FcεRI-dependent mast cell activation.

Genotoxic and cytotoxic drugs, widely used in anticancer therapy, target proliferating cells and induce cell death through a variety of cell cycle-dependent mechanisms. The mechanisms of the delayed toxicity induced by chemotherapy are not fully understood. The accumulation of senescent cells may underlie some of the mechanisms for the development of late adverse effects of chemotherapy on muscle tissue. Cellular models are necessary for the development of therapeutic approaches to these side effects. In our study we used human immortalized myoblast MB135 to optimize the protocol for obtaining the senescent phenotype of muscle cells under the influence of chemotherapeutic drugs such as doxorubicin, cisplatin and arsenic trioxide (As₂O₃). We evaluated the dynamics of changes in senescence proteins pRb, p21 and p53 and SASP-associated proteins such as TNF, IL-1b, IL-6, IL-8, CXCL2, GDF15 using Western blot, RT-PCR and ELISA. Cell senescence was confirmed by the measurement of cell senescence index by flow cytometry after 7 days of exposure to chemotherapeutic agents. The obtained results indicate that all three investigated chemotherapeutic compounds induce the appearance of senescence markers, but the dynamics of these changes are somewhat different for them, which may reflect differences in the mechanisms of senescence phenotype induction.

Urban dust particles are a major pathogenic factor in respiratory diseases such as asthma and chronic obstructive pulmonary disease, and also increase the

Mast cells (MCs) are an important population of connective tissue cells that play a key role in the development of allergic diseases. The main pathway of MC activation in allergies is associated with the interaction of antigen complexes with immunoglobulin E and their subsequent binding to the FcεRI receptor. This leads to rapid release of secretory granules and cytokine production. In recent years, there has been increasing evidence for the involvement of autophagy in many processes, including MC function. Therefore, autophagy regulators can be used as potential inhibitors of MC activity and as therapeutic agents for the treatment of allergic diseases. In the present study, we investigated the effects of two autophagy inhibitors SBI-0206965 and LY294002, and one autophagy activator rapamycin on FcεRI-dependent activation of RBL-2H3, which usually used as model of MCs and basophils. Cell activation was assessed by determining the content of the secretory granule marker β-hexosaminidase and the levels of the cytokines TNF, IL-4 and IL-13. Treatment of cells with SBI-0206965 and LY294002 was shown to reduce FcεRI-dependent degranulation and IL-4 cytokine secretion by RBL-2H3 cells, while the use of rapamycin resulted in reduction of the level of IL-13 cytokine. This indicates the prospect of potential application of these autophagy regulators in the therapy of allergic diseases.