The possible involvement of calcium ions in the regulatory effect of oxidized glutathione on 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.…”

“…Earlier we have shown for the first time that glu toxim and molixan increase the intracellular concen tration of Ca 2+ ([Ca 2+ ] i ), causing mobilization of Ca 2+ from thapsigargin sensitive Ca 2+ stores and subse quent Ca 2+ entry into rat peritoneal macrophages [2][3][4]. 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].…”

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

“…Glutoxim or molixan induced Ca 2+ entry in the cells occurs, presumably, by store dependent mecha nism (Krutetskaya et al, 2007a. Earlier, using purinergic agonists ATP and UTP and endoplasmic Ca 2+ ATPase inhibitors (thapsigargin and cyclopiaz onic acid) we demonstrated that store dependent Ca 2+ entry in rat peritoneal macrophages occurred according to the "secretion like coupling model" of store dependent Ca 2+ entry (Patterson et al, 1999; which supposed the reversible translocation of Ca 2+ store to plasmalemma provided by the actin filaments.…”

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].…”

“…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].…”