Role of Rac GTPase activating proteins in regulation of NADPH oxidase in human neutrophils

Lörincz, Ákos M.; Szarvas, G.; Smith, Susan; Ligeti, Erzsébet

doi:10.1016/j.freeradbiomed.2013.12.001

Cited by 13 publications

(23 citation statements)

References 67 publications

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“…In an acellular system, Rho family GAPs associated with the cell membrane of human neutrophils have been specifically depleted by antibodies, and changes in the NADPH oxidase activity were followed. 6 Extraction of p50RhoGAP (Cdc42GAP) or ARHGAP25 Human (cell free) NADPH oxidase [6] Human/cell culture Phagocytosis Actin polymerization [7,8] ARHGAP1/Cdc42GAP/ p50RhoGAP/RHOGAP1…”

Section: How Many Rho Family Gaps Are Involved In Organizing a Funcmentioning

confidence: 99%

“…Rac/Rho Human (cell free) NADPH oxidase [6,9,11] Mouse No role in integrin-mediated neutrophil functions and in rheumatoid arthritis [12] Human β2 integrin activation [13] ARHGAP46/GMIP RhoA Mouse/human Azurophilic granule exocytosis. [14] ARHGAP15 Rac Mouse Migration, NADPH oxidase, phagocytosis, abdominal sepsis, retention in bone marrow [15,16] Human/cell culture Migration, actin polymerization [17] ARHGAP13/srGAP1 Cdc42 Mouse/human Neutrophil chemotaxis [18] BCR/ABR Rac/Cdc42 Mouse (double knockout) Acute inflammatory responses [19] BCR Rac/Cdc42 Human (cell free) NADPH oxidase [9] Mouse Septic shock NADPH oxidase [20] ARHGAP12 Rac Human/cell culture Actin polymerization [8] ARHGAP43/SH3BP1 Rac Human/cell culture Actin polymerization [8] ARHGAP21/ ARHGAP10…”

Section: How Many Rho Family Gaps Are Involved In Organizing a Funcmentioning

confidence: 99%

“…According to her analysis, the Rac-p67 phox complex allows room to accommodate the GAP domain; thus, a tripartite arrangement could be possible. 6 This model suggests that the GAP could have access to RacGTP also in complex with its target proteinat least with p67 phox -and really terminate the Rac-regulated process. Experimental data showing an increase in superoxide production upon inhibition of GAP action after the assembly of the NADPH oxidase complex has occurred are in agreement with the suggestions of this model.…”

Section: Are Gaps Lonely Players?mentioning

confidence: 99%

“…Experimental data showing an increase in superoxide production upon inhibition of GAP action after the assembly of the NADPH oxidase complex has occurred are in agreement with the suggestions of this model. 34 Moreover, the steric model of the tripartite complex revealed an interface between the target protein p67 phox and the GAP protein, 6 which could serve as selectivity filter for the interacting Rho family GAP. This situation would then be similar to the tripartite structures described for smg-target protein-GEF interactions.…”

Section: Are Gaps Lonely Players?mentioning

confidence: 99%

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The neglected terminators: Rho family GAPs in neutrophils

Csépányi-Kömi

Pásztor

Bartos

et al. 2018

Eur J Clin Investigation

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Background: GTPase-activating proteins (GAPs) accelerate the rate of hydrolysis of GTP bound to small GTPases, thereby limiting the prevalence and concentration of the active, GTP-bound form of these proteins. The large number of potential GAPs acting on members of the Rho family of small GTPases raises the question of specificity or redundancy. Results: In this review, we summarize experimental data obtained on the role of Rho family GAPs in neutrophils, highlight cases where more than one GAP is involved in a physiological function and show examples that GAPs can be involved not only in termination but also in initiation of cellular processes. We demonstrate that the expression-level regulation of GAPs may also occur in shortliving cells such as neutrophils. Finally, we provide insight into the existence and structure of molecular complexes in which Rho family GAPs are involved. Conclusion: GAPs play more complex and varied roles than being simple terminators of cellular processes. K E Y W O R D SGTPase activating proteins, Rho-family small GTPases, neutrophils

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Section: How Many Rho Family Gaps Are Involved In Organizing a Funcmentioning

confidence: 99%

Section: How Many Rho Family Gaps Are Involved In Organizing a Funcmentioning

confidence: 99%

Section: Are Gaps Lonely Players?mentioning

confidence: 99%

Section: Are Gaps Lonely Players?mentioning

confidence: 99%

See 2 more Smart Citations

The neglected terminators: Rho family GAPs in neutrophils

Csépányi-Kömi

Pásztor

Bartos

et al. 2018

Eur J Clin Investigation

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“…We also demonstrated that ARHGAP25 serves as a negative regulator of phagocytosis and related superoxide production (21,22). The aim of the current study was to reveal the role of ARHGAP25 in the complex process of leukocyte recruitment during inflammation.…”

mentioning

confidence: 89%

Rac GTPase Activating Protein ARHGAP25 Regulates Leukocyte Transendothelial Migration in Mice

Csépányi-Kömi

Wisniewski

Bartos

et al. 2016

The Journal of Immunology

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ARHGAP25 is a Rac-specific GTPase-activating protein that is expressed primarily in hematopoietic cells. The involvement of ARHGAP25 in regulating the recruitment of leukocytes to inflammatory sites was investigated in genetically modified mice. Using intravital microscopy, we show that Arhgap25 deficiency affects all steps of leukocyte recruitment with a predominant enhancement of transendothelial migration of neutrophilic granulocytes. Increased transmigration of Arhgap25-deficient leukocytes is demonstrated in inflamed cremaster muscle venules, in a peritonitis model, and in an in vitro chemotaxis assay. Using bone marrow chimeric mice lacking ARHGAP25 in the hematopoietic compartment, we show that enhanced migration in the absence of ARHGAP25 is due to defective leukocyte function. In search for potential mechanisms of ARHGAP25-regulated migration of neutrophils, we detected an increase in the amount of active, GTP-bound Rac and Rac-dependent cytoskeletal changes in the absence of ARHGAP25, suggesting a critical role of ARHGAP25 in counterbalancing the Rac-activating effect of nucleotide exchange factors. Taken together, using Arhgap25-deficient mice, we identified ARHGAP25 as a relevant negative regulator of leukocyte transendothelial migration.

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Nutraceuticals and mitochondrial oxidative stress: bridging the gap in the management of bronchial asthma

Allam

Paudel

Gupta

et al. 2022

Environ Sci Pollut Res

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Asthma is a chronic inflammatory disease primarily characterized by inflammation and reversible bronchoconstriction. It is currently one of the leading causes of morbidity and mortality in the world. Oxidative stress further complicates the pathology of the disease. The current treatment strategies for asthma mainly involve the use of anti-inflammatory agents and bronchodilators. However, long-term usage of such medications is associated with severe adverse effects and complications. Hence, there is an urgent need to develop newer, novel, and safe treatment modalities for the management of asthma. This has therefore prompted further investigations and detailed research to identify and develop novel therapeutic interventions from potent untapped resources. This review focuses on the significance of oxidative stressors that are primarily derived from both mitochondrial and non-mitochondrial sources in initiating the clinical features of asthma. The review also discusses the biological scavenging system of the body and factors that may lead to its malfunction which could result in altered states. Furthermore, the review provides a detailed insight into the therapeutic role of nutraceuticals as an effective strategy to attenuate the deleterious effects of oxidative stress and may be used in the mitigation of the cardinal features of bronchial asthma.

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Role of Rac GTPase activating proteins in regulation of NADPH oxidase in human neutrophils

Cited by 13 publications

References 67 publications

The neglected terminators: Rho family GAPs in neutrophils

The neglected terminators: Rho family GAPs in neutrophils

Rac GTPase Activating Protein ARHGAP25 Regulates Leukocyte Transendothelial Migration in Mice

Nutraceuticals and mitochondrial oxidative stress: bridging the gap in the management of bronchial asthma

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