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Nox generated ROS, particularly those derived from Nox1, Nox2 and Nox4, have emerged as important regulators of the actin cytoskeleton and cytoskeleton-supported cell functions, such as migration and adhesion. The effects of Nox-derived ROS on cytoskeletal remodeling may be largely attributed to the ability of ROS to directly modify proteins that c...
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Citations
... These proteins containing thiols with a low pKa are the targets of the oxidants such as H 2 O 2 . H 2 O 2 could regulate the actin dynamics by oxidation and diminishing its polymerization [27]. The changes affecting the cytoskeleton directly affect cell morphology and cell mechanics. ...
Microglia are the resident macrophage population of the central nervous system. So, microglial cells are a powerful model for studying the mechanism of inflammatory responses. For 70 years, Oscillococcinum®, a homeopathic medicine, has been used for influenza-like illnesses. However, to date its mechanism of action is still unknown. In this study, we investigated the effect of Oscillococcinum 200K dilution in lipopolysaccharide-activated microglial cells in vitro. Inflammation with lipopolysaccharide induces a high production of reactive oxygen species in the cells and Oscillococcinum 200K dilution significantly reduced this production. In order to explain how Oscillococcinum 200K dilution induced this anti-oxidant effect, we decided to study its effect on cell stiffness using Atomic Force Microscopy. In the literature, Atomic Force Microscopy data on cells provides evidence of mechanical changes of cellular structures with different treatments. Atomic Force Microscopy data showed that Oscillococcinum 200K dilution immediately increased the cell stiffness of microglial cells and enhanced the reorganization of actin filaments.
... The migration and adhesion of osteocytes on the material surface are depend on the actin filaments [17,28,29]. Actin filaments at the leading edge of the cell forms lamellar and filamentous pseudopods, generating a force to propel cell migration [30]. ...
... Only ATP-bound actin monomers can form actin filaments with normal function [30]. However, oxidative stress damages the function of mitochondrial to produce ATP [29]. In the present study, high glucose-induced oxidative stress was accompanied by a decrease in the number of pseudopods and migration ability of osteoblasts, while gastrodin reversed the overproduction of ROS and prompted cells to extend many pseudopods. ...
Objective
To investigate the effects of gastrodin on the biological behavior of osteoblasts and osseointegration on the surface of the titanium plate in a high glucose environment, and to explore the possible regulatory mechanisms involved.
Methods
A high glucose-induced oxidative damage model of MC3T3-E1 cells was established in vitro to observe the effects of gastrodin on cellular oxidative stress, cell viability, osteogenic differentiation, mineralization, migration, and adhesion ability on the titanium surface.
Results
High glucose environment can cause oxidative stress damage to MC3T3-E1 cells, leading to a decrease in cell viability, osteogenesis, migration, adhesion and other functions. Gastrodin can upregulate the expression of antioxidant enzymes (Nrf2 and HO-1) and osteogenic differentiation related proteins (RUNX2 and BMP2) in MC3T3-E1 cells in high glucose environment, thereby inhibiting the excessive production of intracellular reactive oxygen species (ROS), reversing the decrease in cell viability, and improving the osteogenic differentiation and mineralization ability of osteoblasts. And gastrodin alleviated the decline in cell migration ability, improved the morphology of the cytoskeleton and increased the adhesion ability of osteoblasts on the surface of titanium plates in high glucose environment. However, gastrodin itself did not affect the cell viability, osteogenic differentiation and mineralization ability of osteoblasts in normal environment.
Conclusions
Gastrodin may protect MC3T3-E1 cells osteogenesis and osseointegration on the surface of the titanium plate in vitro by upregulating antioxidant enzymes expression, and attenuating high glucose-induced oxidative stress. Therefore, gastrodin may be a potential drug to address the problem of poor implant osseointegration in patients with diabetes.
... . Nox-derived ROS can regulate important cellular functions supported by the cytoskeleton (Valdivia et al., 2015;Xu et al., 2017). In this context, the current Research Topic features two articles highlighting the relevance of Nox enzymes during actin cytoskeleton dynamics. ...
... The oxidation of Cys-374 is reported to lead to a decrease in the polymerization and elongation rate of F-actin filaments [43], while oxidation of the Met-44 residue of actin by the flavoprotein monooxygenase Mical causes disassembly and decreased polymerization of actin filaments [44]. NADPH oxidase enzymes have been found to localize with actin leading to the proposal that the cytoskeleton can be both regulated by ROS and play a role in its localized production [45]. ...
In this chapter, we describe the discovery of the NADPH oxidase gene and protein of the single-celled yeast Saccharomyces cerevisiae, Yno1. This enzyme was characterized with respect to mechanism of action, subcellular location, regulation of gene expression, and physiological function. Yno1 is not involved in defense and is not highly expressed in vegetatively growing cells. However, it is expressed in diverse stress situations. The signaling substance produced by Yno1 in conjunction with the superoxide dismutase Sod1, hydrogen peroxide, consequently leads through a change in the expression of target genes to the modulation of an adaptive cellular response. An example is the formation of pseudohyphae enabling invasive growth of the yeast cells, which is believed to aid in the utilization of new nutrients. The major role of Yno1 is in the switch of the mode of growth from vegetative budding to the formation of pseudohyphae, which are elongated chains of cells. Further examples that are described in this chapter are the response to osmotic stress and mating. All these pathways have in common that they exit the regular cell cycle and are associated with in parts enormous changes in cell morphology. This is accomplished involving a change in the structure of the actin cytoskeleton. Yno1 was shown to directly modulate the actin cytoskeleton.KeywordsNADPH oxidaseOxidative stressPseudohyphal growthMatingOsmotic stressActin cytoskeletonActin bodies
... Several important processes for the correct function of platelets are related to the NOX function. NOX2 affects lamellipodium formation as well as cytoskeleton rearrangement and cell adhesion function [50]. Platelets, due to NOX, responding to environmental stimuli produce and release ROS, such as O 2 ...
Oxidative stress participates at the baseline of different non-communicable pathologies such as cardiovascular diseases. Excessive formation of reactive oxygen species (ROS), above the signaling levels necessary for the correct function of organelles and cells, may contribute to the non-desired effects of oxidative stress. Platelets play a relevant role in arterial thrombosis, by aggregation triggered by different agonists, where excessive ROS formation induces mitochondrial dysfunction and stimulate platelet activation and aggregation. Platelet is both a source and a target of ROS, thus we aim to analyze both the platelet enzymes responsible for ROS generation and their involvement in intracellular signal transduction pathways. Among the proteins involved in these processes are Protein Disulphide Isomerase (PDI) and NADPH oxidase (NOX) isoforms. By using bioinformatic tools and information from available databases, a complete bioinformatic analysis of the role and interactions of PDI and NOX in platelets, as well as the signal transduction pathways involved in their effects was performed. We focused the study on analyzing whether these proteins collaborate to control platelet function. The data presented in the current manuscript support the role that PDI and NOX play on activation pathways necessary for platelet activation and aggregation, as well as on the platelet signaling imbalance produced by ROS production. Our data could be used to design specific enzyme inhibitors or a dual inhibition for these enzymes with an antiplatelet effect to design promising treatments for diseases involving platelet dysfunction.
... Low concentrations of hydrogen peroxide (H 2 O 2 ) can additionally polymerise actin by a non-nucleation pathway [19]. The importance of functional ROS levels has been especially characterized in cellular migration where the leading edge of a migrating cell requires higher ROS production than the trailing edge to ensure dynamic cytoskeletal remodeling [20,21]. Too little ROS production is detrimental to actin remodeling. ...
Cellular prion protein (PrPC) protects neurons against oxidative stress damage. This role is lost upon its misfolding into insoluble prions in prion diseases, and correlated with cytoskeletal breakdown and neurophysiological deficits. Here we used mouse neuronal models to assess how PrPC protects the neuronal cytoskeleton, and its role in network communication, from oxidative stress damage. Oxidative stress was induced extrinsically by potassium superoxide (KO2) or intrinsically by Mito-Paraquat (MtPQ), targeting the mitochondria. In mouse neural lineage cells, KO2 was damaging to the cytoskeleton, with cells lacking PrPC (PrP-/-) damaged more than wild-type (WT) cells. In hippocampal slices, KO2 acutely inhibited neuronal communication in WT controls without damaging the cytoskeleton. This inhibition was not observed in PrP-/- slices. Neuronal communication and the cytoskeleton of PrP-/- slices became progressively disrupted and degenerated post-recovery, whereas the dysfunction in WT slices recovered in 5 days. This suggests that the acute inhibition of neuronal activity in WT slices in response to KO2 was a neuroprotective role of PrPC, which PrP-/- slices lacked. Heterozygous expression of PrPC was sufficient for this neuroprotection. Further, hippocampal slices from mice expressing PrPC without its GPI anchor (PrPGPI-/-) displayed acute inhibition of neuronal activity by KO2. However, they failed to restore normal activity and cytoskeletal formation post-recovery. This suggests that PrPC facilitates the depressive response to KO2 and its GPI anchoring is required to restore KO2-induced damages. Immuno spin-trapping showed increased radicals formed on the filamentous actin of PrP-/- and PrPGPI-/- slices, but not WT and PrP+/- slices, post-recovery suggesting ongoing dysregulation of redox balance in the slices lacking GPI-anchored PrPC. The MtPQ treatment of hippocampal slices temporarily inhibited neuronal communication independent of PrPC expression. Overall, GPI-anchored PrPC alters synapses and neurotransmission to protect and repair the neuronal cytoskeleton, and neuronal communication, from extrinsically induced oxidative stress damages.
... The actin cytoskeleton must be finely tuned, which is energetically costly, both in space and time, to fulfill key cellular functions such as cell division, cell shape changes, phagocytosis, and cell migration [91,92]. For example, during osseointegration, the migration, adhesion, and morphology of osteocytes on the surface of the material depend heavily on the assembly/de-assembly of actin filaments. ...
Gastrodin, a traditional Chinese medicine ingredient, is widely used to treat vascular and neurological diseases. However, recently, an increasing number of studies have shown that gastrodin has anti-osteoporosis effects, and its mechanisms of action include its antioxidant effect, anti-inflammatory effect, and anti-apoptotic effect. In addition, gastrodin has many unique advantages in promoting bone healing in tissue engineering, such as inducing high hydrophilicity in the material surface, its anti-inflammatory effect, and pro-vascular regeneration. Therefore, this paper summarized the effects and mechanisms of gastrodin on osteoporosis and bone regeneration in the current research. Here we propose an assumption that the use of gastrodin in the surface loading of oral implants may greatly promote the osseointegration of implants and increase the success rate of implants. In addition, we speculated on the potential mechanisms of gastrodin against osteoporosis, by affecting actin filament polymerization, renin–angiotensin system (RAS) and ferroptosis, and proposed that the potential combination of gastrodin with Mg2+, angiotensin type 2 receptor blockers or artemisinin may greatly inhibit osteoporosis. The purpose of this review is to provide a reference for more in-depth research and application of gastrodin in the treatment of osteoporosis and implant osseointegration in the future.
... The scheme of ROS endogenous and exogenous sources, their functions in an organism, and undesirable consequences of ROS excess. also take part in cytoskeletal regulation and cytoskeleton-supported cell functions, such as migration and adhesion (San Martín and Griendling, 2010;Wilson and González-Billault, 2015;Valdivia et al., 2015) (left part of Fig. 1). ...
Biological oxidation processes are in the core of life energetics, play an important role in cellular biophysics, physiological cell signaling or cellular pathophysiology. Understanding of biooxidation processes is also crucial for biotechnological applications.
Therefore, a plethora of methods has been developed for monitoring oxidation so far, each with distinct advantages and disadvantages. We review here the available methods for monitoring oxidation and their basic characteristics and capabilities. Then we focus on a unique method - the only one that does not require input of additional external energy or chemicals - which employs detection of biological autoluminescence (BAL). We highlight the pros and cons of this method and provide an overview of how BAL can be used to report on various aspects of cellular oxidation processes starting from oxygen consumption to the generation of oxidation products such as carbonyls. This review highlights the application potential of this completely non-invasive and label-free biophotonic diagnostic method.
... However, previous studies reported that ZnO NPs lead to alterations in the cytoskeletal protein of keratinocytes, epithelial cells [44], and spermatogonia [1]. ZnO NPs lead to the overproduction of ROS, which can influence the cytoskeleton through the oxidation of cytoskeletal proteins [45]. Therefore, immunoblotting analysis was performed to determine whether a compound (chalcone 1) with antioxidant activity could protect cytoskeletal proteins from oxidative stress during exposure to ZnO NPs (Figure 7). ...
Zinc oxide nanoparticles (ZnO NPs) are one of the most used nanoparticles due to their unique physicochemical and biological properties. There is, however, a growing concern about their negative impact on male reproductive health. Therefore, in the present study, two different strategies were used to evaluate the recovery ability of spermatogonia cells from the first stage of spermatogenesis (GC-1 spg cell line) after being exposed to a cytotoxic concentration of ZnO NPs (20 µg/mL) for two different short time periods, 6 and 12 h. The first strategy was to let the GC-1 cells recover after ZnO NPs exposure in a ZnO NPs-free medium for 4 days. At this phase, cell viability assays were performed to evaluate whether this period was long enough to allow for cell recovery. Exposure to ZnO NPs for 6 h and 12 h induced a decrease in viability of 25% and 41%, respectively. However, the recovery period allowed for an increase in cell viability from 16% to 25% to values as high as 91% and 84%. These results strongly suggest that GC-1 cells recover, but not completely, given that the cell viability does not reach 100%. Additionally, the impact of a synthetic chalcone (E)-3-(2,6-dichlorophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one (1) to counteract the reproductive toxicity of ZnO NPs was investigated. Different concentrations of chalcone 1 (0-12.5 µM) were used before and during exposure of GC-1 cells to ZnO NPs to mitigate the damage induced by NPs. The protective ability of this compound was evaluated through viability assays, levels of DNA damage, and cytoskeleton dynamics (evaluating the acetylated α-tubulin and β-actin protein levels). The results indicated that the tested concentrations of chalcone 1 can attenuate the genotoxicity induced by ZnO NPs for shorter exposure periods (6 h). Chalcone 1 supplementation also increased cell viability and stabilized the microtubules. However, the antioxidant potential of this compound remains to be elucidated. In conclusion, this work addressed the main cytotoxic effects of ZnO NPs on a spermatogonia cell line and analyzed two different strategies to mitigate this damage, which represent a significant contribution to the field of male fertility.
... Previously, two classes of oxidases, NOX and Mical, have been reported to regulate F-actin dynamics through actin oxidation 40,41 . The TM9SF family of proteins is reported to have NADH oxidase activity at their NTF 18 and GSH, the latter one also being known as actin glutathionylation. ...
F-actin dynamics is crucial for many fundamental properties of cancer cells, from cell-substrate adhesion to migration, invasion and metastasis. However, the regulatory mechanisms of actin dynamics are still incompletely understood. In this study, we demonstrate the function of a protein named TM9SF4 in regulating actin dynamics and controlling cancer cell motility and metastasis. We show that an N-terminal fragment (NTF) cleaved from TM9SF4 can directly bind to F-actin to induce actin oxidation at Cys374, consequently enhancing cofilin-mediated F-actin disassembly. Knockdown of TM9SF4 reduces cell migration and invasion in ovarian cancer cells A2780, SKOV3 and several high grade serous ovarian cancer lines (HGSOCs). In vivo, knockdown of TM9SF4 completely abolishes the tumor growth and metastasis in athymic nude mice. These data provide mechanistic insights into TM9SF4-mediated regulation of actin dynamics in ovarian cancer cells. F-actin dynamics influence cancer cell motility. Here the authors show that TM9SF4 facilitates the cofilin-induced disassembly of F-actin to promote cancer cell migration and metastasis.
