Focal Adhesion Kinase Regulation by Oxidative Stress in Different Cell Types

Cell shape regulation is important but the mechanisms that govern shape are not fully understood, in part due to limited experimental models where cell shape changes and underlying molecular processes can be rapidly and non-invasively monitored in real time. Here, we use an optogenetic tool to activate RhoA in the middle of mononucleated macrophages to induce contraction, resulting in a side with the nucleus that retains its shape and a non-nucleated side which was unable to maintain its shape and collapsed. In cells overexpressing focal adhesion kinase (FAK), the non-nucleated side exhibited a wide flat morphology and was similar in adhesion area to the nucleated side. In cells overexpressing fascin, an actin bundling protein, the non-nucleated side assumed a spherical shape and was similar in height to the nucleated side. This effect of fascin was also observed in fibroblasts even without inducing furrow formation. Based on these results, we conclude that FAK and fascin work together to maintain cell shape by regulating adhesion area and height, respectively, in different cell types.

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Focal Adhesion Kinase Regulation of Mechanotransduction and its Impact on Endothelial Cell Functions

Microvascular Research ◽

10.1016/j.mvr.2011.06.007 ◽

2012 ◽

Vol 83 (1) ◽

pp. 71-81 ◽

Cited By ~ 74

Author(s):

Noureddine Zebda ◽

Oleksii Dubrovskyi ◽

Konstantin G. Birukov

Keyword(s):

Endothelial Cell ◽

Focal Adhesion Kinase ◽

Focal Adhesion ◽

Kinase Regulation ◽

Cell Functions

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Differential activation of focal adhesion kinase, Rho and Rac by the ninth and tenth FIII domains of fibronectin

Journal of Cell Science ◽

10.1242/jcs.112.17.2937 ◽

1999 ◽

Vol 112 (17) ◽

pp. 2937-2946

Author(s):

N.A. Hotchin ◽

A.G. Kidd ◽

H. Altroff ◽

H.J. Mardon

Keyword(s):

Growth Factor ◽

Focal Adhesion Kinase ◽

Signaling Pathways ◽

Focal Adhesion ◽

Cell Attachment ◽

Cell Types ◽

Integrin Receptors ◽

3T3 Cells ◽

Swiss 3T3 ◽

Kinase Phosphorylation

Fibronectins are widely expressed extracellular matrix ligands that are essential for many biological processes. Fibronectin-induced signaling pathways are elicited in diverse cell types when specific integrin receptors bind to the ninth and tenth FIII domains, FIII9-10. Integrin-mediated signal transduction involves activation of signaling pathways of the growth factor-dependent Ras-related small GTP-binding proteins Rho and Rac, and phosphorylation of focal adhesion kinase. We have dissected the requirement of FIII9 and FIII10 for Rho and Rac activity and phosphorylation of focal adhesion kinase in BHK fibroblasts and Swiss 3T3 cells. We demonstrate that FIII10 supports cell attachment but does not induce phosphorylation of focal adhesion kinase. In Swiss 3T3 cells, growth factor-independent phosphorylation of focal adhesion kinase and downstream adhesion events are dependent upon the presence of FIII9 in the intact FIII9-10 pair, whereas FIII10-mediated focal adhesion kinase phosphorylation requires a synergistic signal from growth factors. Furthermore, FIII10 is able to elicit cellular responses mediated by Rho, but not Rac, whereas FIII9-10 can elicit both Rho- and Rac-mediated responses. We propose that activation of specific integrin subunits by the FIII10 and FIII9-10 ligands elicits distinct signaling events. This may represent a general molecular mechanism for activation of receptor-specific signaling pathways by a multi-domain ligand.

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Oxidative Stress, Neuroinflammation and Mitochondria in the Pathophysiology of Amyotrophic Lateral Sclerosis

Antioxidants ◽

10.3390/antiox9090901 ◽

2020 ◽

Vol 9 (9) ◽

pp. 901 ◽

Cited By ~ 3

Author(s):

Elena Obrador ◽

Rosario Salvador ◽

Rafael López-Blanch ◽

Ali Jihad-Jebbar ◽

Soraya L. Vallés ◽

...

Keyword(s):

Oxidative Stress ◽

Amyotrophic Lateral Sclerosis ◽

Cell Types ◽

T Cell Subsets ◽

Cellular Interactions ◽

Underlying Mechanisms ◽

Different Cell Types ◽

And Oxidative Stress ◽

Different Levels ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron (MN) disease. Its primary cause remains elusive, although a combination of different causal factors cannot be ruled out. There is no cure, and prognosis is poor. Most patients with ALS die due to disease-related complications, such as respiratory failure, within three years of diagnosis. While the underlying mechanisms are unclear, different cell types (microglia, astrocytes, macrophages and T cell subsets) appear to play key roles in the pathophysiology of the disease. Neuroinflammation and oxidative stress pave the way leading to neurodegeneration and MN death. ALS-associated mitochondrial dysfunction occurs at different levels, and these organelles are involved in the mechanism of MN death. Molecular and cellular interactions are presented here as a sequential cascade of events. Based on our present knowledge, the discussion leads to the idea that feasible therapeutic strategies should focus in interfering with the pathophysiology of the disease at different steps.

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Focal adhesion kinase PTK2 autophosphorylation is not required for the activation of sodium–hydrogen exchange by decreased cell volume in the preimplantation mouse embryo

Zygote ◽

10.1017/s0967199419000212 ◽

2019 ◽

Vol 27 (3) ◽

pp. 173-179

Author(s):

Jane C. Fenelon ◽

Baozeng Xu ◽

Jay M. Baltz

Keyword(s):

Focal Adhesion Kinase ◽

Cell Volume ◽

Focal Adhesion ◽

Mouse Embryo ◽

Hydrogen Exchange ◽

Cell Types ◽

Mouse Embryos ◽

Cell Stage ◽

Early Embryos ◽

Early Mouse

SummaryRecovery from decreased cell volume is accomplished by a regulated increase of intracellular osmolarity. The acute response is activation of inorganic ion transport into the cell, the main effector of which is the Na+/H+ exchanger NHE1. NHE1 is rapidly activated by a cell volume decrease in early embryos, but how this occurs is incompletely understood. Elucidating cell volume-regulatory mechanisms in early embryos is important, as it has been shown that their dysregulation results in preimplantation developmental arrest. The kinase JAK2 has a role in volume-mediated NHE1 activation in at least some cells, including 2-cell stage mouse embryos. However, while 2-cell embryos show partial inhibition of NHE1 when JAK2 activity is blocked, NHE1 activation in 1-cell embryos is JAK2-independent, implying a requirement for additional signalling mechanisms. As focal adhesion kinase (FAK aka PTK2) becomes phosphorylated and activated in some cell types in response to decreased cell volume, we sought to determine whether it was involved in NHE1 activation in the early mouse embryo. FAK activity requires initial autophosphorylation of a tyrosine residue, Y397. However, FAK Y397 phosphorylation levels were not increased in either 1- or 2-cell embryos after cell volume was decreased. Furthermore, the selective FAK inhibitor PF-562271 did not affect NHE1 activation at concentrations that essentially eliminated Y397 phosphorylation. Thus, autophosphorylation of FAK Y397 does not appear to be required for NHE1 activation induced by a decrease in cell volume in early mouse embryos.

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Evaluation of Oxidative Stress Biomarkers in Brain Metastatic and Non-Metastatic Lung Cancer Patients with Different Cell Types

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210211163055 ◽

2021 ◽

Vol 21 ◽

Author(s):

Emre Bilgin ◽

Gülüzar Atli ◽

Berna Bozkurt Duman ◽

Ali I. Okten

Keyword(s):

Oxidative Stress ◽

Lung Cancer ◽

Cancer Patients ◽

Antioxidant System ◽

Cell Types ◽

Oxidative Stress Biomarkers ◽

Lung Cancer Patients ◽

Stress Biomarkers ◽

Metastatic Lung ◽

Different Cell Types

Background : Oxidative stress lead to an imbalanced prooxidant/antioxidant status can be a critical factor affecting the lung cancer etiopathology. The antioxidant system provides primary protection under oxidative stress. Objective: The purpose of the study was to investigate the serum antioxidant system status in brain metastatic and non-metastatic lung cancer patients with different cell types. Methods: In this prospective study, 33 patients with lung cancer metastasis (metastatic patient group), 36 lung cancer patients (non-metastatic patient group) and 25 healthy control groups were included. Enzymatic (superoxide dismutase, SOD; glutathione peroxidase, GPX; and glutathione reductase, GR) and non-enzymatic (glutathione, GSH) antioxidant system biomarkers with thiobarbituric acid reactive substances (TBARS) levels were studied in the serum samples of the control and patient groups. The oxidative stress biomarkers were measured spectrophotometrically. Results: SOD activity increased though TBARS levels and GR activity decreased in both patient groups compared to the control. GPX activity increased only in the non-metastatic group. Antioxidant biomarkers varied between small cell and non-small cell group patients. GR activity and GSH levels were significantly higher in the non-metastatic group compared to the metastatic group. There were also found correlations between antioxidant parameters in the non-metastatic group. Conclusions: It was emphasized the imbalanced antioxidant system in the duration of the disease related to not only cell type and also the metastatic structure. This is the preliminary study exhibiting the contribution of antioxidant imbalance in different subtypes with varied prognosis and behavior of lung cancer in the presence of brain metastasis. Therefore, oxidative stress biomarkers can serve as a useful tool to get information about the progression of lung cancer. Thus it may provide fundamental data for further cancer researches when considering the diagnosis of the disease.

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