The role of tyrosine kinases and tyrosine phosphatases in the effect of glutoxim and oxidized glutathione on the intracellular Ca2+ concentration in macrophages

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

“…Thus in T lymphocytes with defective protein WAVE2 activating the Arp2/3 complex one observes suppression of store dependent Ca 2+ entry activated by thapsigargin [22]. The above results, along with our previous findings [2][3][4][5][6][7][8][9][10][11] testify about that in the action of glutoxim or molixan on [Ca 2+ ] i in macrophages the same signal proteins and their complexes as in the process of exocytosis are involved: tyrosine kinases, G proteins of small molec ular mass, mechanisms of vesicular transport; actin and tubulin cytoskeleton, and also Arp2/3 complex mediating rearrangements of the actin cytoskeleton. Reorganization of the actin cytoskeleton induced in macrophages upon action of glutoxim or molixan may also mediate activation of macrophages and alleviate processes of endo and exocytosis.…”

“…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].…”

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

“…Later we demonstrated that the same effect on [Ca 2+ ] i is observed in macrophages treated with molixan (Krutetskaya et al, 2010). In addition, it was found that tyrosine kinases, tyrosine phosphatases (Krutetskaya et al, 2007b, phosphatidylinositol kinases , small G proteins from Ras family as well as phospholipase C and protein kinase C, the key mole cules of phosphoinositol signaling pathway are the critical components of the signaling cascade, triggered by GSSG and glu toxim and leading to [Ca 2+ ] i increase in macrophages.…”

Involvement of small G proteins and vesicle traffic in the glutoxim and molixan effects on the intracellular Ca2+ concentration in macrophages

“…Glutoxim and molixan belong to the phar macological group of thiopoetines, which affect intra cellular redox regulation. However, the cellular and molecular mechanisms of their action are insuffi ciently understood.In our previous studies, it was first shown that GSSG, glutoxim, and molixan increased the intracel lular Ca 2+ concentration ([Ca 2+ ] i ) in rat peritoneal macrophages by mobilizing calcium ions from thapsi gargin sensitive Ca 2+ stores and subsequently stimu lating the Ca 2+ uptake [2][3][4].Using a wide range of agents affecting different components of intracellular signaling systems, we first identified the principal elements of the signal cascade triggered by GSSG and glutoxim and resulting in a [Ca 2+ ] i increase in macrophages, namely, tyrosine kinases and tyrosine phosphatases [3,5], phosphati dylinositol kinases [6], and the key enzymes of the phosphoinositide signaling system, phospholipase C and protein kinase C [7]. It was also found that the effects of glutoxim and molixan on [Ca 2+ ] i in mac rophages were mediated by actin cytoskeleton ele ments [8] and microtubules [9].…”

“…Using a wide range of agents affecting different components of intracellular signaling systems, we first identified the principal elements of the signal cascade triggered by GSSG and glutoxim and resulting in a [Ca 2+ ] i increase in macrophages, namely, tyrosine kinases and tyrosine phosphatases [3,5], phosphati dylinositol kinases [6], and the key enzymes of the phosphoinositide signaling system, phospholipase C and protein kinase C [7]. It was also found that the effects of glutoxim and molixan on [Ca 2+ ] i in mac rophages were mediated by actin cytoskeleton ele ments [8] and microtubules [9].…”