Arachidonic acid signaling to the cytoskeleton: The role of cyclooxygenase and cyclic AMP‐dependent protein kinase in actin bundling

Glenn, Honor L.; Jacobson, Bernard

doi:10.1002/cm.10072

Cited by 22 publications

(27 citation statements)

References 31 publications

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“…Formation of these actin bundles also was found to require myosin activation via myosin light chain kinase (MLCK) activity [Glenn and Jacobson, 2002]. Activated myosin polymerizes into filaments, which can then associate with actin to form contractile structures [Goeckeler and Wysolmerski, 1995].…”

Section: Introductionmentioning

confidence: 98%

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Cyclooxygenase and cAMP‐dependent protein kinase reorganize the actin cytoskeleton for motility in HeLa cells

Glenn

Jacobson

2003

Cell Motil. Cytoskeleton

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The adhesion of a cell to its surrounding matrix is a key determinant in many aspects of cell behavior. Adhesion consists of distinct stages : attachment, cell spreading, motility, and/or immobilization. Interrelated signaling pathways regulate these stages, and many adhesion-related signals control the architecture of the cytoskeleton. The various cytoskeletal organizations then give rise to the specific stages of adhesion. It has been shown that arachidonic acid acts at a signaling branch point during cell attachment. Arachidonic acid is metabolized via lipoxygenase to activate actin polymerization and cell spreading. It is also metabolized by cyclooxygenase to generate small actin bundles. We have used confocal microscopy and indirect immunofluorescence to investigate the structure of these cyclooxygenase dependent actin bundles in HeLa cells. We have also employed cell migration assays and pharmacological modulation of cyclooxygenase and downstream signals. The results indicate that cyclooxygenase and PKA stimulate the formation of actin bundles that contain myosin II and associate with small focal adhesions. In addition, we demonstrate that this cytoskeletal organization correlates with increased cell motility.

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Section: Introductionmentioning

confidence: 98%

“…Prostaglandin E 2 (PGE 2 ) was determined to signal adenylate cyclase to generate cyclic AMP (cAMP) and activate PKA. This branch of AA signaling causes polymerized actin to reorganize into small bundles [Glenn and Jacobson, 2002].…”

Section: Introductionmentioning

confidence: 99%

Cyclooxygenase and cAMP‐dependent protein kinase reorganize the actin cytoskeleton for motility in HeLa cells

Glenn

Jacobson

2003

Cell Motil. Cytoskeleton

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“…For example, leukotriene D4 enhanced the binding of Caco-2 cells to Collagen I by increasing a2b1 integrin expression. 13 AA metabolization by Lox, but not Cox, was required for subsequent PKC 14,15 and Rho-GTPase activation to properly direct remodeling of the actin cytoskeleton during cell spreading on collagen. 16 We recently reported a DPI-inhibitable ROS production occurring during cell adhesion and spreading of Caco-2 cells.…”

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confidence: 94%

Nox1 downstream of 12‐lipoxygenase controls cell proliferation but not cell spreading of colon cancer cells

Carvalho

Sadok

Bourgarel-Rey

et al. 2007

Intl Journal of Cancer

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The catalytic subunit of the NADPH oxidase complex, Nox1 (homologue of gp91phox/Nox2), expressed mainly in intestinal epithelial and vascular smooth muscle cells, functions in innate immune defense and cell proliferation. The molecular mechanisms underlying these functions, however, are not completely understood. We measured Nox1-dependent O 2 2 production during cell spreading on Collagen IV (Coll IV) in colon carcinoma cell lines. Knocking down Nox1 by shRNA, we showed that Nox1-dependent O 2 2 production is activated during cell spreading after 4 hr of adhesion on Collagen IV. Nox1 activation during cell spreading relies on Rac1 activation and arachidonic metabolism. Our results showed that manoalide (a secreted phospholipase A2 inhibitor) and cinnamyl-3,4-dihydroxy-a-cyanocinnamate (a 12-lipoxygenase inhibitor) inhibit O 2 2 production, cell spreading and cell proliferation in these colonic epithelial cells. 12-Lipoxygenase inhibition of ROS production and cell spreading can be reversed by adding 12-HETE, a 12-lipoxygenase product, supporting the specific effect observed with cinnamyl-3,4-dihydroxy-a-cyanocinnamate. In contrast, Nox1 shRNA and DPI (NADPH oxidase inhibitor) weakly affect cell spreading while inhibiting O 2 2 production and cell proliferation. These results suggest that the 12-lipoxygenase pathway is upstream of Nox1 activation and controls cell spreading and proliferation, while Nox1 specifically affects cell proliferation. ' 2007 Wiley-Liss, Inc.Key words: NADPH oxidase; Nox1; colon; integrins; arachidonic acidThe phagocytic NADPH oxidase is composed of 5 subunits, including p22phox and gp91 phox that constitute the membranebound flavocytochrome b 558 , and p40 phox , p47phox and p67 phox that translocate from the cytoplasm to the membrane upon cell activation.1 In addition, the small Rac GTPase have emerged as important functional components that are indispensable for NADPH oxidase activity. Since the initial identification of Nox1 (gp91 phox homolog) in human Caco-2 colon carcinoma cells, the biological significance of superoxide production by NAPDH oxidase in nonphagocytic cells has garnered much interest.2 In contrast to gp91phox/Nox2, which catalyzes a massive and explosive production of superoxide involved in host defense, Nox1 controls a lower superoxide production that acts as mediator of cell signaling. 2Nox1 is expressed mainly in normal and cancerous intestinal epithelial cells and vascular smooth muscle cells. Although being the subject of intense investigation, the role and the endogenous regulation of Nox1 in colon epithelial cells is still unclear.3,4 In colon carcinoma cells, homologs of p47 phox and p67 phox , respectively called Noxo1 (for Nox organizer 1) and Noxa1 (for Nox activator 1), have recently been identified. 5,6 In contrast to p47phox , Noxo1 appears to be constitutively associated with the NADPH oxidase complex.Activation of NADPH oxidase is dependent upon lipid mediators, such as phosphatidic and arachidonic acids and phosphatidylinositol. Arachidonic acid (AA)...

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“…It is known that actin filaments mostly exist in the cytoplasm in the form of a bundle, and PKA plays a role in the bundling of actin filaments [8,9,12]. Therefore, it is considered that in blastocysts whose PKA activity has been inhibited, hatching will be suppressed and changes will occur in the hatching process and contraction.…”

Section: Discussionmentioning

confidence: 99%

“…Using HeLa cells, Glenn and Jacobson [8,9] have clarified that the activity of protein kinase C (PKC) triggers actin polymerization leading to cell spreading and that the action of protein kinase A (PKA) leads to bundling of polymerized actin (actin filaments) in the cortical cytoplasm, and this cytoskeletal organization correlates with cell motility. In blastocysts, it is also believed that trophectoderm cell motility is involved in hatching through the action of actin filaments [10,11].…”

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confidence: 99%

Hatching and Distribution of Actin Filaments in Mouse Blastocysts Whose Activities of Protein Kinase A were Suppressed by H-89

Suzuki

Niimura

2010

Journal of Reproduction and Development

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Abstract. The role of actin filaments and contractions in hatching was determined in mouse blastocysts whose actin filament bundling abilities had been suppressed by H-89, an inhibitor of protein kinase A. The hatching rate of blastocysts developed from morulae in a medium containing H-89 at a concentration of 4.0 μM was 17.2%, which was significantly lower than the 76.7% of the control blastocysts developed from morulae in a medium without H-89. The rates of blastocysts starting hatching and forming a slit in the zona pellucida were significantly lower in H-89-treated blastocysts (84.4 and 21.9%) than in control blastocysts (100.0 and 90.6%). The lengths of time needed for slit formation in the zona pellucida and for completion of hatching were significantly longer in the H-89-treated blastocysts (27.4 and 43.3 h) than in the control blastocysts (6.5 and 18.8 h). Over the course of 32 h after blastocoel formation, the number of strong contractions was similar in the H-89-treated and control blastocysts, but the number of weak contractions was significantly fewer in the H-89-treated blastocysts (2.41 times) than in the control blastocysts (4.19 times). Although the distribution of actin filaments was similar in the H-89-treated and control blastocysts in the pre-hatching, hatching and post-hatching periods, the rate of H-89-treated blastocysts in which most trophectoderm cells possessed the fluorescence of actin filaments (12.7%) was significantly lower than the 95.0% of the control blastocysts in the prehatching period. These results suggest that actin filament-mediated movements of trophectoderm cells contribute to hatching by facilitating the protrusion of trophectoderm cells from a small hole in the zona pellucida and by enlarging the protrusion. We also suggest that the low hatching ability of the treated blastocysts is related to weak contractions with a low frequency and to strong contractions requiring a longer time for re-expansion.

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Arachidonic acid signaling to the cytoskeleton: The role of cyclooxygenase and cyclic AMP‐dependent protein kinase in actin bundling

Cited by 22 publications

References 31 publications

Cyclooxygenase and cAMP‐dependent protein kinase reorganize the actin cytoskeleton for motility in HeLa cells

Cyclooxygenase and cAMP‐dependent protein kinase reorganize the actin cytoskeleton for motility in HeLa cells

Nox1 downstream of 12‐lipoxygenase controls cell proliferation but not cell spreading of colon cancer cells

Hatching and Distribution of Actin Filaments in Mouse Blastocysts Whose Activities of Protein Kinase A were Suppressed by H-89

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