Calmodulin inhibitors, W-7 and TFP, block the calmodulin-independent activation of NADPH-oxidase by arachidonate in a cell-free system

Sakata, Atsuko; Ida, E Holm; Tominaga, Mari; Onoue, Kaoru

doi:10.1016/0006-291x(87)91083-7

Cited by 9 publications

(4 citation statements)

References 15 publications

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“…Thus, it may be tempting to speculate that calmodulin-rather than PKC-mediated reactions are involved in NADPH oxidase activation by PMA and FMLP [26]. There is, however, no additional evidence that PMA activates NADPH oxidase via calmodulin [2], Interestingly, it was recently reported that TFP and W-7 but not H-7 strongly inhibited the PKC-and calmodulin-independent activation of NADPH oxidase in cell-free systems [7,27]. These data suggest that W-7 and TFP may be potent inhibitors of NADPH oxidase per …”

Section: Discussionmentioning

confidence: 99%

Stimulus-dependent inhibition of platelet aggregation by the protein kinase C inhibitors polymyxin B, H-7 and staurosporine

Schächtele¹,

Seifert

Oßwald³

1988

Biochemical and Biophysical Research Communications

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The effects of various protein kinase C (PKC) inhibitors on NADPH oxidase (NO) activation by the phorbol ester PMA and by the chemotactic peptide FMLP were studied. H-7 reduced the effects of both stimuli in human neutrophils (HN) and HL-60 cells by 13-63%. Polymyxin B did not inhibit NO activation by PMA and FMLP in HN and reduced the effects of both stimuli in HL-60 cells by 27-55%. Retinal and retinoic acid enhanced the effects of PMA and FMLP in HL-60 cells and of FMLP in HN up to 4.5-fold. In contrast, retinoic acid inhibited the effect of PMA in HN, In the presence of cytochalasin B, retinal inhibited the effect of FMLP in HN, whereas retinoic acid inhibited NO activation by FMLP in both cell types. The dual PKC/calmodulin inhibitors trifluoperazine and W-7 abolished NO activation by PMA and FMLP in HN and HL-60 cells. Thus, the effects of PKC inhibitors on NO activation exhibit (I) cell type specificity, (2) stimulus dependency and (3) no correlation with in vitro inhibition of PKC. Our results suggest that studies with PKC inhibitors presently available cannot clarify the role of PKC in NO activation. ~1988Ac~d .... Press, Inc.Human neutrophils possess an NADPH oxidase which catalyzes 0 2" formation and can be activated by cell-permeable diacylglycerol and PMA via PKC [I,2] and by the chemotactic peptide, FMLP [3]. The mechanism by which FMLP activates 0 2 -formation is not known. There is a debate concerning the involvement of PKC in cellular activation by FMLP [3]. In recent studies, certain PKC

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Section: Discussionmentioning

confidence: 99%

Stimulus-dependent inhibition of platelet aggregation by the protein kinase C inhibitors polymyxin B, H-7 and staurosporine

Schächtele¹,

Seifert

Oßwald³

1988

Biochemical and Biophysical Research Communications

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“…The three different calmodulin inhibitors block Ca 2+ -dependent binding of calmodulin to substrates and were employed to evaluate the role of calmodulin in the interaction between Pyk2 and PSD-95, as well as Pyk2 activation, at the following concentrations: W7 (10 µM), TFP (20 µM), and calmidazolium (30 µM) (Schweitzer, 1987; Wakamori et al, 1993; Della Rocca et al, 1997; Liu et al, 1999; Heidinger et al, 2002). W7 is a member of the naphthalene-sulphonamide class of drugs, which also appears to block NADPH oxidase activation by arachidonate (Sakata et al, 1987). TFP, a member of the phenothiazine family, is the best characterized calmodulin antagonist as crystal structures have been solved illustrating its interaction with calmodulin (Cook et al, 1994; Vandonselaar et al, 1994).…”

Section: Methodsmentioning

confidence: 99%

Postsynaptic Clustering and Activation of Pyk2 by PSD-95

Bartos¹,

Ulrich²,

Li³

et al. 2010

J. Neurosci.

124

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The tyrosine kinase Pyk2 plays a unique role in intracellular signal transduction by linking Ca 2ϩ influx to tyrosine phosphorylation, but the molecular mechanism of Pyk2 activation is unknown. We report that Pyk2 oligomerization by antibodies in vitro or overexpression of PSD-95 in PC6-3 cells induces trans-autophosphorylation of Tyr402, the first step in Pyk2 activation. In neurons, Ca 2ϩ influx through NMDA-type glutamate receptors causes postsynaptic clustering and autophosphorylation of endogenous Pyk2 via Ca 2ϩ -and calmodulin-stimulated binding to PSD-95. Accordingly, Ca 2ϩ influx promotes oligomerization and thereby autoactivation of Pyk2 by stimulating its interaction with PSD-95. We show that this mechanism of Pyk2 activation is critical for long-term potentiation in the hippocampus CA1 region, which is thought to underlie learning and memory.

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“…Although calmodulin has been suggested to be involved in the exocytotic process, the inhibitory mechanisms of these agents is still unclear, since calmodulin is involved in diverse cellular structures and functions. Moreover, it is uncertain that these compounds act only on calmodulin (Sakata et al, 1987). The interpretation of the present findings seems to be very simple.…”

Section: Amylase Releasementioning

confidence: 99%

Evidence against direct involvement of cyclic AMP-dependent protein phosphorylation in the exocytosis of amylase

Teratani

1988

Biochemical Journal

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To examine whether or not the activation of cyclic AMP-dependent protein kinase is coupled to the exocytosis of amylase from rat parotid cells, the effect of protein kinase inhibitors on amylase release and protein phosphorylation was studied. A membrane-permeable inhibitor of cyclic AMP-dependent protein kinase, N-[2-(methylamino)ethyl]-5-isoquinolinesulphonamide (H-8), and peptide fragments of the heat-stable protein kinase inhibitor [PKI-(5-24)-peptide and PKI-(14-24)-amide] strongly inhibited cyclic AMP-dependent protein kinase activity in the cell homogenate. However, H-8 had no inhibitory effect on amylase release from either intact or saponin-permeabilized parotid cells stimulated by isoproterenol or cyclic AMP. Moreover, PKI-(5-24)-peptide and PKI-(14-24)-amide did not inhibit cyclic AMP-evoked amylase release from saponin-permeabilized cells, whereas cyclic AMP-dependent phosphorylations of 21 and 26 kDa proteins in intact or permeabilized cells were markedly inhibited by these inhibitors. These results suggest that cyclic AMP-dependent protein phosphorylation is not directly involved in the exocytosis of amylase regulated by cyclic AMP.

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Calmodulin inhibitors, W-7 and TFP, block the calmodulin-independent activation of NADPH-oxidase by arachidonate in a cell-free system

Cited by 9 publications

References 15 publications

Stimulus-dependent inhibition of platelet aggregation by the protein kinase C inhibitors polymyxin B, H-7 and staurosporine

Stimulus-dependent inhibition of platelet aggregation by the protein kinase C inhibitors polymyxin B, H-7 and staurosporine

Postsynaptic Clustering and Activation of Pyk2 by PSD-95

Evidence against direct involvement of cyclic AMP-dependent protein phosphorylation in the exocytosis of amylase

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