Role of MAPK ERK1/2 and p38 in the Realization of Growth Potential of Various Types of Regeneration-Competent Cells in Mouse Neural Tissue during Ethanol-Induced Neurodegeneration In Vitro

Halogenated (Cl-ion) songorine is a new original agonist of fibroblast growth factor receptors of neuronal-committed progenitors possessing neuroregenerative effect after cerebral ischemia and hypoxia in experimental animals

“…In this case, the index of differentiation of neuronal-committed progenitors was at the level of that in the culture of cells without addition of FGF. The obtained results corresponded to the literature data about the properties of the investigated early-growth factor which help to stimulate the functions of progenitors [14,19]. The study of the participation of individual signaling molecules in the realization of proliferative-differentiating potential of clonogenic PSA-NCAM + cells under the influence of mSON and FGF revealed a number of specific characteristics of intracellular signaling for each of FGFR agonists.…”

“…Moreover, it is the secretion of neurotrophic factor that can be the basis of the detected phenomenon of direct anti-ischemic activity of the alkaloid in the early periods after hypoxia. At the same time, a number of significant differences in intracellular transduction happened under the influence of mSON on cells in comparison with FGF was revealed [14,33]. Unlike FGF, the modified alkaloid, in addition to proliferation, significantly stimulates the differentiation of progenitor cells.…”

“…Inhibitors of individual signaling molecules and their concentrations were used in the experiment: NF-кB «oridonine» (1 μM); NF-кB, IKK, PKC «aurothiomalate» (50 μM); PI3K «LY294002» (50 μM); ERK1/2 «PD98059» (100 μM); p38 and PKB «SB203580» (10 μM); adenylate cyclase «2',5'dideoxyadenosine» (30 μM); IKK-2 «Inhibitor IV» (2 μM); JNK «SP600125» (10 μM); p53 (5 μM) (Pifithrin-, Cyclic); JAK1.3 «CP 690550» (blocks JAK1 or JAK3, depending on the concentration of 1 nM and 100 nM, respectively); JAK2 was induced with AG 490 (50 μM); STAT3 «STAT3 Inhibitor XIV, LLL12» (5 μM). The working concentrations of the antagonists in vitro were determined in accordance with instructions of the developers of these chemical agents and confirmed as the optimum in own preliminary experiments on the test cultures [14,[27][28][29][30][31]. The specimens of nervous tissue were taken from subventricular area of cerebral hemispheres.…”

“…In this case more physiological and perspective approach to solving the problems of regenerative medicine, including treatment of central nervous system diseases, is considered to be pharmacological stimulation of endogenous SC functions by imitation of the activity of natural regulatory systems [7]. During development of "Pharmacological strategy of regenerative medicine" at the Goldberg Research Institute of Pharmacology and Regenerative Medicine the principal possibility and high effectiveness of this approach to the therapy of a number of diseases, including pathological conditions of the central nervous system, were demonstrated in the experiment [1, 6, 7, [14][15][16][17][18][19].…”

“…We isolated the diterpene alkaloid of tizidine-type songorine and revealed its stimulating effect on the mesenchymal progenitors associated with the effect on receptors for the growth factor of fibroblasts (FGFR) [18,19]. The important role of this pleiotropic early-acting growth factor in the definition of proliferativedifferentiation status of cells, including NSC, is known [14,20,21].…”