Arachidonic Acid Induces Direct Interaction of the p67 -Rac Complex with the Phagocyte Oxidase Nox2, Leading to Superoxide Production

Matono, Rumi; Miyano, Kei; Kiyohara, Takuya; Sumimoto, Hideki

doi:10.1074/jbc.m114.581785

Cited by 40 publications

(33 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, neither inhibition of FLAP nor inhibition of prostaglandin synthesis by the COX-2 antagonist nimesulide blunted AA-induced ROS generation. This suggests that ROS may arise from the direct stimulation of NADPH oxidase by AA, as has been previously demonstrated for NOX1 in human colon adenocarcinoma cells [Sadok et al, 2008], NOX2 in HeLa cells [Matono et al, 2014], and NOX4 in human fibroblasts [Rossary et al, 2007]. Our data confirm the results of our previous studies showing that ROS, namely from NOX1 and NOX4, are critically involved in the regulation of vascular differentiation of murine ES cells [Sauer et al, 2005;Schmelter et al, 2006;.…”

supporting

confidence: 91%

“…Previous studies have indicated that AA induces ROS generation in cells [Chien et al, 2013] and cell-free systems [Souabni et al, 2012] via interaction of the p67(phox)-Rac complex with the phagocyte oxidase Nox2 [Matono et al, 2014]. Moreover, our studies have demonstrated that ROS are critically involved in vasculogenesis of ES cells [Sauer et al, 2005;Bekhite et al, 2010].…”

Section: Ros Generation In Embryoid Bodies Upon Aa Treatmentsupporting

confidence: 70%

“…The mechanism by which AA increases ROS generation may involve different sources, which include LOX and COX as well as NADPH oxidases [Cho et al, 2011;Speed and Blair, 2011]. Recently, it has been demonstrated that AA induces superoxide generation in human HeLa cells via direct interaction of the p67(phox)-Rac complex with the phagocyte oxidase Nox2 [Matono et al, 2014]. Moreover, stimulation of ROS production downstream of BLT1 and BLT2 signaling has been reported in different leukocyte cell types and cancer cells, and was mainly attributed to the activation of the NOX1 isoform of NADPH oxidase [Cho et al, 2011].…”

mentioning

confidence: 99%

See 2 more Smart Citations

Impact of Arachidonic Acid and the Leukotriene Signaling Pathway on Vasculogenesis of Mouse Embryonic Stem Cells

Huang

Sharifpanah

Becker

et al. 2016

Cells Tissues Organs

View full text Add to dashboard Cite

Embryonic stem (ES) cells can differentiate into various kinds of cells, such as endothelial and hematopoietic cells. In addition, some evidence suggests that inflammatory mediators such as leukotrienes (LTs), which include the 5-lipoxygenase (LOX) family, can regulate endothelial cell differentiation. In the present study, the eicosanoid precursor arachidonic acid (AA) stimulated vasculogenesis of ES cells by increasing the number of fetal liver kinase-1+ vascular progenitor cells as well as vascular structures positive for platelet endothelial cell adhesion protein-1 and vascular endothelial cadherin. The stimulation of vasculogenesis and expression of the rate-limiting enzyme in the LT signaling pathway, 5-LOX-activating protein (FLAP), was blunted upon treatment with the FLAP inhibitors AM643 and REV5901. Vasculogenesis was significantly restored upon exogenous addition of LTs. Downstream of FLAP, the LTB₄ receptor (BLT1) blocker U75302, the BLT2 receptor blocker LY255283 as well as the cysteinyl LT blocker BAY-u9773 inhibited vasculogenesis of ES cells. AA treatment of differentiating ES cells increased reactive oxygen species (ROS) generation, which was not affected upon either FLAP or cyclooxygenase-2 inhibition. Prevention of ROS generation by either the free radical scavengers vitamin E and N-(2-mercaptopropionyl)glycine or the NADPH oxidase inhibitor VAS2870 downregulated vasculogenesis of ES cells and blunted the provasculogenic effect of AA. In summary, our data demonstrate that proinflammatory AA stimulates vasculogenesis of ES cells via the LT pathway by mechanisms involving ROS generation.

show abstract

supporting

confidence: 91%

Section: Ros Generation In Embryoid Bodies Upon Aa Treatmentsupporting

confidence: 70%

mentioning

confidence: 99%

See 1 more Smart Citation

Impact of Arachidonic Acid and the Leukotriene Signaling Pathway on Vasculogenesis of Mouse Embryonic Stem Cells

Huang

Sharifpanah

Becker

et al. 2016

Cells Tissues Organs

View full text Add to dashboard Cite

show abstract

“…Other studies on cPLA2 knockout mice suggested this phospholipase had no role in Nox2 activation [56], consistent with the dependence of murine Nox2 on the phospholipase A2 activity of Prdx6. Arachidonate and other soluble amphiphiles activate cell-free reconstitution of Nox2 and may act in promoting assembly and activation of Nox2 in whole cells by inducing structural changes in p47 phox and p67 phox that enable their interaction with membrane oxidase components, p22 phox and Nox2, respectively [57] [58]. Arachidonate or sodium dodecyl sulfate can also induce changes in Noxo1 that promote its interaction with p22 phox [14] [16].…”

Section: Discussionmentioning

confidence: 99%

Peroxiredoxin 6 (Prdx6) supports NADPH oxidase1 (Nox1)-based superoxide generation and cell migration

Kwon

Wang

Burke

et al. 2016

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Nox1 is an abundant source of reactive oxygen species (ROS) in colon epithelium recently shown to function in wound healing and epithelial homeostasis. We identified Peroxiredoxin 6 (Prdx6) as a novel binding partner of Nox activator 1 (Noxa1) in yeast two-hybrid screening experiments using the Noxa1 SH3 domain as bait. Prdx6 is a unique member of the Prdx antioxidant enzyme family exhibiting both glutathione peroxidase and phospholipase A2 activities. We confirmed this interaction in cells overexpressing both proteins, showing Prdx6 binds to and stabilizes wild type Noxa1, but not the SH3 domain mutant form, Noxa1 W436R. We demonstrated in several cell models that Prdx6 knockdown suppresses Nox1 activity, whereas enhanced Prdx6 expression supports higher Nox1-derived superoxide production. Both peroxidase- and lipase-deficient mutant forms of Prdx6 (Prdx6 C47S and S32A, respectively) failed to bind to or stabilize Nox1 components or support Nox1-mediated superoxide generation. Furthermore, the transition-state substrate analogue inhibitor of Prdx6 phospholipase A2 activity (MJ-33) was shown to suppress Nox1 activity, suggesting Nox1 activity is regulated by the phospholipase activity of Prdx6. Finally, wild type Prdx6, but not lipase or peroxidase mutant forms, supports Nox1-mediated cell migration in the HCT-116 colon epithelial cell model of wound closure. These findings highlight a novel pathway in which this antioxidant enzyme positively regulates an oxidant-generating system to support cell migration and wound healing.

show abstract

“…However, a careful study of the cPLA 2 null mouse demonstrated that this enzyme has minimal effect on activation of NOX2 in response to agonists [141]. Further, the role of arachidonate in NOX2 activation proved to be primarily an in vitro phenomenon, although arachidonic acid (as well as other unsaturated fatty acids) may bind to components of the NOX2 complex in vivo to stabilize their expression [142]. Subsequent attention focused on lysophospholipid as the product of PLA 2 activity that is required for NOX2 activation.…”

Section: Physiological Roles Of Prdx6mentioning

confidence: 99%

Peroxiredoxin 6 in the repair of peroxidized cell membranes and cell signaling

Fisher

2017

Archives of Biochemistry and Biophysics

148

127

View full text Add to dashboard Cite

Peroxiredoxin 6 represents a widely distributed group of peroxiredoxins that contain a single conserved cysteine in the protein monomer (1-cys Prdx). The cys when oxidized to the sulfenic form is reduced with glutathione (GSH) catalyzed by the π isoform of GSH-S-transferase. Three enzymatic activities of the protein have been described:1) peroxidase with H2O2, short chain hydroperoxides, and phospholipid hydroperoxides as substrates; 2) phospholipase A2 (PLA2); and 3) lysophosphatidylcholine acyl transferase (LPCAT). These activities have important physiological roles in antioxidant defense, turnover of cellular phospholipids, and the generation of superoxide anion via initiation of the signaling cascade for activation of NADPH oxidase (type 2). The ability of Prdx6 to reduce peroxidized cell membrane phospholipids (peroxidase activity) and also to replace the oxidized sn-2 fatty acyl group through hydrolysis/reacylation (PLA2 and LPCAT activities) provides a complete system for the repair of peroxidized cell membranes.

show abstract

Arachidonic Acid Induces Direct Interaction of the p67 -Rac Complex with the Phagocyte Oxidase Nox2, Leading to Superoxide Production

Cited by 40 publications

References 66 publications

Impact of Arachidonic Acid and the Leukotriene Signaling Pathway on Vasculogenesis of Mouse Embryonic Stem Cells

Impact of Arachidonic Acid and the Leukotriene Signaling Pathway on Vasculogenesis of Mouse Embryonic Stem Cells

Peroxiredoxin 6 (Prdx6) supports NADPH oxidase1 (Nox1)-based superoxide generation and cell migration

Peroxiredoxin 6 in the repair of peroxidized cell membranes and cell signaling

Contact Info

Product

Resources

About