The involvement of actin cytoskeleton in glutoxim and molixan effect on intracellular Ca2+-concentration in macrophages

Kurilova, L. S.; Krutetskaya, Z. I.; Lebedev, O. E.; Krutetskaya, N. I.; Антонов, В. Г.

doi:10.1134/s1990519x12030066

Cited by 9 publications

(15 citation statements)

References 20 publications

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“…The results of the present work are in agreement with our data on participation of the actin cytoskele ton in the action of glutoxim or molixan on [Ca 2+ ] i and data that glutoxim and molixan themselves cause reor ganization of the actin cytoskeleton in macrophages [8]. In intact macrophages the elements of actin cytoskeleton are localized under the plasma mem brane and form a distinctly distinguished cortical layer, while in cells treated with glutoxim or molixan, the cortical layer becomes broader and "looser" and there appeared clusters of actin in the cytosol [8].…”

Section: Resultssupporting

confidence: 92%

“…In intact macrophages the elements of actin cytoskeleton are localized under the plasma mem brane and form a distinctly distinguished cortical layer, while in cells treated with glutoxim or molixan, the cortical layer becomes broader and "looser" and there appeared clusters of actin in the cytosol [8]. Thus, reorganization of the actin cytoskeleton upon the action of glutoxim or molixan appears to be a neces sary condition for signal transduction from plasmale mma to intracellular Ca 2+ stores and development of Ca 2+ mobilization from stores.…”

Section: Resultsmentioning

confidence: 99%

“…Apart from that, it has been disclosed that glutoxim or molixan themselves cause reorganization of the actin cytoskeleton in macrophages: the cortical layer becomes broader and "looser" and there appear clus ters of actin in the cytosol [8]. Also we have shown the involvement of G proteins of small molecular mass of the Ras superfamily and processes of vesicular trans port in the effect of glutoxim or molixan on [Ca 2+ ] i in macrophages [10,11].…”

Section: Introductionmentioning

confidence: 86%

“…Using a wide range of agents affecting components of intracellular signaling systems in cells, we have shown for the first time that key players in a signal cas cade triggered by GSSG and glutoxim and leading to [Ca 2+ ] i increase in macrophages are tyrosine kinases and tyrosine phosphatases [3,5], phosphatidylinositol kinases [6], key enzymes of the phosphoinositide sig nal pathway -phospholipase C and protein kinase C [7]. It was also found that the effect of glutoxim and molixan on [Ca 2+ ] i in macrophages was mediated by actin cytoskeleton [8] and microtubules [9].…”

Section: Introductionmentioning

confidence: 90%

“…Calcium free medium differed in that it contained 1 mM EGTA and did not contain CaCl 2 . In detail the procedure of cul tivating macrophages was described earlier [8].…”

Section: Cellsmentioning

confidence: 99%

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Arp2/3 complex is involved in the effect of glutoxim and molixan on intracellular Ca2+ concentration in macrophages

et al. 2014

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The involvement of Arp2/3 complex, which causes actin filament branching, in the effect of drugs glutoxim and molixan on intracellular Ca 2+ concentration was investigated. Using Fura 2AM microfluorim etry it was shown for the first time that Arp2/3 complex inhibitor CK 0944666 almost completely prevents the increase in intracellular Ca 2+ concentration, induced by glutoxim or molixan in macrophages. The data suggest the involvement of Arp2/3 complex in the glutoxim and molixan effect on the Ca 2+ signaling pro cesses in macrophages.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 90%

“…Calcium free medium differed in that it contained 1 mM EGTA and did not contain CaCl 2 . In detail the procedure of cul tivating macrophages was described earlier [8].…”

Section: Cellsmentioning

confidence: 99%

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Arp2/3 complex is involved in the effect of glutoxim and molixan on intracellular Ca2+ concentration in macrophages

et al. 2014

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Haloperidol, a Sigma-1 Receptor Antagonist, Inhibits Ca2+ Responses in Rat Peritoneal Macrophages

Milenina,

Krutetskaya,

Antonov

et al. 2023

BIOPHYSICS

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Involvement of microtubules in the effects of glutoxim and molixan on the intracellular concentration of Ca2+ in macrophages

et al. 2013

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196Currently, a great number of disulfide containing drugs altering the redox status and having a physiolog ically significant effect on cells have been developed and introduced into clinical practice. The pharmaceu tical agent Glutoxim®, disodium salt of oxidized glu tathione (GSSG) with a platinum nanoadditive (PHARMA VAM, Moscow, Russia) is used as an immunomodulator and a hemostimulant in the inte grated therapy of bacterial and viral diseases, psoriasis, as well as radio and chemotherapies of cancer [1]. Another disulfide containing agent, molixan (a com plex of glutoxim and inosine nucleoside), has a similar application. However, the mechanisms of the cellular and molecular effects of these drugs are not com pletely understood.We were the first to find out earlier that GSSG, glu toxim, and molixan enhance the intracellular Са 2+ concentration ([Ca 2+ ] i ) due to Са 2+ mobilization from the thapsigargin sensitive Са 2+ stores and subsequent entry of Са 2+ into rat peritoneal macrophages [2][3][4]. Using a wide range of agents affecting the components of signaling systems in cells, we have demonstrated that tyrosine kinases, tyrosine phosphatases [3, 5], phosphatidylinositol kinases [6], small G proteins of the Ras superfamily, and the most important enzymes of the phosphoinositide system of signal transduction (phospholipase C and protein kinase C) [7] are the key players in the signaling cascade triggered by GSSG and glutoxim and leading to an increase in [Ca 2+ ] i in mac rophages. It has also been found that elements of the actin cytoskeleton are involved in the effects of glutoxim and molixan on [Ca 2+ ] i in macrophages [8,9].It is known that the microtubule protein tubulin has a high redox sensitivity and can be easily S glu tathionylated [10]. Correspondingly, it was reasonable to study the possible role of microtubules in the regu latory effect of glutoxim or molixan on [Ca 2+ ] i in the rat peritoneal macrophages.The procedure of macrophage culturing and an automated system for [Ca 2+ ] i recording with the use of the fluorescent probe Fura 2AM were described ear lier in detail [11]. The experiments were performed at a room temperature of 20-22°C on the second or third day of cell culturing. The involvement of micro tubules in the effects of glutoxim and molixan on [Ca 2+ ] i in the rat peritoneal macrophages was studied using two structurally different agents capable of inducing depolymerization of microtubules, colcemid and nocodazole, as well as the microtubule stabilizer taxol [12].It has been demonstrated that incubation of mac rophages in the presence of 100 µg/mL molixan (Fig. 1a) or 100 µg/mL glutoxim (Fig. 2a) for 20 min in a medium without calcium causes a significant increase in [Ca 2+ ] i , which reflects mobilization of Са 2+ from intracellular Са 2+ stores. Addition of 2 mM Са 2+ to the external medium induces entry of Са 2+ into the cytosol, which is apparently mediated by depletion of the Са 2+ store (Figs. 1a, 2a).It has been found that nocodazole, colcemid, or taxol almost complet...

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The involvement of actin cytoskeleton in glutoxim and molixan effect on intracellular Ca2+-concentration in macrophages

Cited by 9 publications

References 20 publications

Arp2/3 complex is involved in the effect of glutoxim and molixan on intracellular Ca2+ concentration in macrophages

Arp2/3 complex is involved in the effect of glutoxim and molixan on intracellular Ca2+ concentration in macrophages

Haloperidol, a Sigma-1 Receptor Antagonist, Inhibits Ca2+ Responses in Rat Peritoneal Macrophages

Involvement of microtubules in the effects of glutoxim and molixan on the intracellular concentration of Ca2+ in macrophages

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