Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) plays various important roles in the physiological system. With regard to chemotaxis of neutrophils, there are reports that endogenous NO is a mediator of chemotaxis, and others that exogenous NO inhibits chemotaxis. It is also reported that NO itself expressed chemotactic activity. On the other hand, we have recently proposed the importance of cofilin, an actin-binding phosphoprotein, in phagocyte functions through dephosphorylation and translocation to the plasma membrane regions. Because chemotaxis is a phenomenon of dynamic cell movement, cofilin, a regulator of the cytoskeletal system, may be involved in its mechanisms. To clarify further the effect of NO on functions of leukocytes and to examine the effect of NO on cofilin, we investigated the chemotaxis of neutrophil-like HL-60 cells induced by NO, as well as the influence of NO on the phosphorylation and intracellular distribution of cofilin. Two NO donors, 3-[2-hydroxy-1-(1-methylethyl)-2-nitrosohydrazino]-1-propanamin e (NOC5) and S-nitroso-N-acetylpenicillamine (SNAP), were shown to cause chemotaxis, and, 2-(4-carboxyphenyl)-4,4,5, 5-tetramethylimidazole-1-oxyl 3-oxide (carboxy-PTIO), a NO-specific scavenger, inhibited the chemotaxis induced by NO-donors, suggesting that NO itself released from the NO donors has chemotactic activity. LY-83583 and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), inhibitors of soluble guanylate cyclase, inhibited the chemotaxis to NO donors, which implies that soluble guanylate cyclase is involved in the signaling pathway of this NO action. We also found that NO caused translocation of cofilin to the cell periphery, though dephosphorylation of cofilin was not detected. These results demonstrate that NO has chemotactic activity for neutrophils and caused the translocation of cofilin to the plasma membrane regions without its dephosphorylation.
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PMID:Nitric oxide induces chemotaxis of neutrophil-like HL-60 cells and translocation of cofilin to plasma membranes. 1109 Jun 94

Angiotensin II (Ang II) has been reported to induce migration in neuronal cell types. Using time-lapse microscopy, we show here that Ang II induces acceleration in NG108-15 cell migration. This effect was antagonized by PD123319, a selective AT2 receptor antagonist, but not by DUP753, a selective AT1 receptor antagonist, and was mimicked by the specific AT2 receptor agonist CGP42112. This Ang II-induced acceleration was not sensitive to the inhibition of previously described signaling pathways of the AT2 receptor, guanylyl cyclase/cyclic GMP or p42/p44 mapk cascades, but was abolished by pertussis toxin treatment and involved PP2A activation. Immunofluorescence studies indicate that Ang II or CGP42112 decreased the amount of filamentous actin at the leading edge of the cells. This decrease was accompanied by a concomitant increase in globular actin levels. Regulation of actin turnover in actin-based motile systems is known to be mainly under the control of the actin depolymerizing factor and cofilin. Basal migration speed decreased by 77.2% in cofilin-1 small interfering RNA-transfected NG108-15 cells, along with suppression of the effect of Ang II. In addition, the Ang II-induced increase in cell velocity was abrogated in serum-free medium as well as by genistein or okadaic acid treatment in a serum-containing medium. Such results indicate that the AT2 receptor increases the migration speed of NG108-15 cells and involves a tyrosine kinase activity, followed by phosphatase activation, which may be of the PP2A type. Therefore, the present study identifies actin depolymerization and cofilin as new targets of AT2 receptor action, in the context of cellular migration.
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PMID:Angiotensin II type 2 receptor stimulation increases the rate of NG108-15 cell migration via actin depolymerization. 1832 1