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At least 19 recordsLinked to original sources
PubMed2004

Conversion of death signal into survival signal by redox signaling.

Reperfusion of ischemic myocardium produces reactive oxygen species (ROS) and results in apoptotic cell death and DNA fragmentation. Several redox-sensitive anti- and pro- apoptotic transcription factors including nuclear factor kappaB (NF-kappaB) and heterodimeric transcription factor AP-1 progressively and steadily increase in the heart as a function of the duration of ischemia and reperfusion. When the heart is adapted to ischemic stress by repeated short-term ischemia and reperfusion, NF-kappaB remains high, while AP-1 is lowered to almost baseline value. The anti-apoptotic gene Bcl-2 is downregulated in the ischemic/reperfused heart, while it is upregulated in the adapted myocardium. Cardioprotective abilities of the adapted myocardium are abolished when heart is pre-perfused with N-acetyl cysteine to scavenge ROS, suggesting a role of redox signaling. Mammalian heart is protected by several defense systems, which include, among others, the redox-regulated protein thioredoxin. Reperfusion of ischemic myocardium results in the downregulation of thioredoxin 1 (Trx 1) expression, which was upregulated in the adapted myocardium. The increased expression of Trx 1 is completely blocked with an inhibitor of Trx 1, cis-diammine-dichloroplatinum, which also abolished cardioprotection afforded by ischemic adaptation. The cardioprotective role of Trx 1 is further confirmed with transgenic mouse hearts overexpressing Trx 1. The Trx 1 mouse hearts displayed significantly improved post-ischemic ventricular recovery and reduced myocardial infarct size and apoptosis compared to the corresponding wild-type mouse hearts. The results of this study implicate a crucial role of redox signaling in transmitting anti-death signal.

Animals↗
PubMed2003

Redox control, redox signaling, and redox homeostasis in plant cells.

Redox chemistry is a key feature of life. Oxidized substrates are reduced to synthesize functional molecules; reduced substrates are oxidized for energy supply. In addition, cells must fight against uncontrolled oxidation of essential constituents, a process that continuously occurs in an atmosphere of 21% O2. The redox situation is further complicated in plants with their highly reactive photosynthetic metabolism. To this end it is now well established that redox regulation is a central element in adjusting plant metabolism and development to the prevailing environmental conditions. This review introduces general redox chemistry and the main components of the cellular redox network, namely pyridine nucleotides, ascorbate, glutathione, lipoic acid, tocopherol, thioredoxins, glutaredoxins, peroxiredoxins, and other thiol proteins. Examples for redox sensing, transduction, redox-regulated enzymes and transcription, and the function of regulatory circuits are presented. Emphasis is placed on redox regulation of photosynthesis, which is the best understood metabolism governed by redox control on essentially all levels, ranging from gene transcription to translation, assembly and turnover, as well as short-term adaptation by state transition and enzyme activity. Increasing evidence shows the importance of redox regulation in the context of transport, plant development, and programmed cell death.

Feedback, Physiological↗
PubMed2006

Redox signalling in anchorage-dependent cell growth.

Current data have provided new perspectives concerning the regulation of non-transformed cell proliferation in response to both soluble growth factors and to adhesive cues. Non-transformed cells are anchorage dependent for the execution of the mitotic program and cannot avoid the concomitant signals starting from mitogenic molecules, as growth factors, and adhesive agents belonging to extracellular matrix. Reactive oxygen species play a key role during both growth factor and integrin receptor signalling and these second messengers are recognised to have a synergistic function for anchorage-dependent growth signalling. Redox regulated proteins include protein tyrosine phosphatases and protein tyrosine kinases, although with opposite regulation of their enzymatic activity, and cytoskeletal proteins as beta-actin. In this review we support a role of ROS as key second messengers granting a proper executed mitosis for anchorage-dependent cells, through redox regulation of several downstream targets. Deregulation of these redox pathways may help to guide transformed cells to elude the native apoptotic response to abolishment of signals started by cell/ECM contact, sustaining ectopic anchorage-independent cancer cell growth.

Animals↗
PubMed2006

Oxidative stress and redox signalling in cardiac hypertrophy and heart failure.

Substantial evidence suggests the involvement of oxidative stress in the pathophysiology of congestive heart failure and its antecedent conditions such as cardiac hypertrophy and adverse remodelling after MI. Oxidative stress describes an imbalance between antioxidant defences and the production of reactive oxygen species (ROS), which at high levels cause cell damage but at lower levels induce subtle changes in intracellular signalling pathways (termed redox signalling). ROS are derived from many sources including mitochondria, xanthine oxidase, uncoupled nitric oxide synthases and NADPH oxidases. The latter enzymes are especially important in redox signalling, being implicated in the pathophysiology of hypertension and atherosclerosis, and activated by diverse pathologically relevant stimuli. We review the contribution of ROS to heart failure pathophysiology and discuss potential therapies that may specifically target detrimental redox signalling. Indeed, drugs such as ACE inhibitors and statins may act in part through such mechanisms. A better understanding of redox signalling mechanisms may enable the development of new targeted therapeutic strategies rather than the non-specific antioxidant approaches that have to date been disappointing in clinical trials.

Heart Failure↗
PubMed2004

Cysteine/cystine couple is a newly recognized node in the circuitry for biologic redox signaling and control.

Redox mechanisms function in control of gene expression, cell proliferation, and apoptosis, but the circuitry for redox signaling remains unclear. Cysteine and methionine are the only amino acids in proteins that undergo reversible oxidation/reduction under biologic conditions and, as such, provide a means for control of protein activity, protein-protein interaction, protein trafficking, and protein-DNA interaction. Hydrogen peroxide and other reactive oxygen species (ROS) provide a mechanism to oxidize signaling proteins. However, oxidation of sulfur-containing side chains of cysteine and methionine by ROS can result in oxidation states of sulfur (e.g., sulfinate, sulfonate, sulfone) that are not reducible under biologic conditions. Thus, mechanisms for oxidation that protect against over-oxidation of these susceptible residues and prevent irreversible loss of activity would be advantageous. The present study shows that the steady-state redox potential of the cysteine/cystine couple (Eh = -145 mV) in cells is sufficiently oxidized (>90 mV) relative to the GSH/GSSG (-250 mV) and thioredoxin (Trx1, -280 mV) redox couples for the cysteine/cystine couple to function as an oxidant in redox switching. Consequently, the cysteine/cystine couple provides a means to oxidize proteins without direct involvement of more potent oxidants. A circuitry model incorporating cysteine as a redox node, along with Trx1 and GSH, reveals how selective interactions between the different thiol/disulfide couples and reactive protein thiols could differentially regulate metabolic functions. Moreover, inclusion of cysteine/cystine as a signaling node distinct from GSH and Trx1 significantly expands the redox range over which protein thiol/disulfide couples may operate to control physiologically relevant processes.

Buthionine Sulfoximine↗
PubMedDate not supplied

Current concepts of redox signaling in the lungs.

In the intracellular redox state (GSH/GSSG) the cell plays a key role in the regulation and potentiation of the inflammatory response in lung cells. Glutathione and thioredoxin are the important protective antioxidants in the lungs. Regulation of intracellular redox glutathione and thioredoxin levels in response to reactive oxygen/nitrogen species and in inflammation should have critical effects on different lung cells on the activation of redox sensor/signal transduction pathways and various transcription factors. Possibly via the modification of cysteine residues, oxidative stress activates multiple stress kinase pathways and transcription factors nuclear factor-kappaB and activator protein-1, which differentially regulate the genes for proinflammatory cytokines as well as the protective antioxidant genes. Emerging data suggest that protein-S-thiolation, protein-S-nitrosation, and oxidation of protein-SH (formation of sulfenic, sulfinic, and sulfonic acids) are critical in redox signaling during normal physiology and under oxidative stress in controlling the cellular processes. In this review, we discuss the recent findings in the context of redox signaling during inflammation, pathology, and the role of redox modulating agents/dietary interventions either to inhibit abnormal signaling or induce/boost the endogenous antioxidant systems. Furthermore, this also provides information as to how antioxidants are involved in redox signaling to control inflammatory and oxidative stress in the lung.

Animals↗
PubMed2003

Redox signaling in the growth and development of colonial hydroids.

Redox signaling provides a quick and efficient mechanism for clonal or colonial organisms to adapt their growth and development to aspects of the environment, e.g. the food supply. A 'signature' of mitochondrial redox signaling, particularly as mediated by reactive oxygen species (ROS), can be elucidated by experimental manipulation of the electron transport chain. The major sites of ROS formation are found at NADH dehydrogenase of complex I and at the interface between coenzyme Q and complex III. Inhibitors of complex III should thus upregulate ROS from both sites; inhibitors of complex I should upregulate ROS from the first but not the second site, while uncouplers of oxidative phosphorylation should downregulate ROS from both sites. To investigate the possibility of such redox signaling, perturbations of colony growth and development were carried out using the hydroid Podocoryna carnea. Oxygen uptake of colonies was measured to determine comparable physiological doses of antimycin A(1) (an inhibitor of complex III), rotenone (an inhibitor of complex I) and carbonyl cyanide m-chlorophenylhydrazone (CCCP; an uncoupler of oxidative phosphorylation). Using these doses, clear effects on colony growth and development were obtained. Treatment with antimycin A(1) results in 'runner-like' colony growth, with widely spaced polyps and stolon branches, while treatment with CCCP results in 'sheet-like' growth, with closely spaced polyps and stolon branches. Parallel results have been obtained previously with azide, an inhibitor of complex IV, and dinitrophenol, another uncoupler of oxidative phosphorylation. Perhaps surprisingly, rotenone produced effects on colony development similar to those of CCCP. Assays of peroxides using 2',7'-dichlorofluorescin diacetate and fluorescent microscopy suggest a moderate difference in ROS formation between the antimycin and rotenone treatments. The second site of ROS formation (the interface between coenzyme Q and complex III) may thus predominate in the signaling that regulates colony development. The fat-rich, brine shrimp diet of these hydroids may be relevant in this context. Acyl CoA dehydrogenase, which catalyzes the first step in the mitochondrial beta-oxidation of fatty acids, carries electrons to coenzyme Q, thus bypassing complex I. These results support a role for redox signaling, mediated by ROS, in colony development. Nevertheless, other redox sensors between complexes I and III may yet be found.

Adaptation, Physiological↗
PubMed2004

Retrograde plastid redox signals in the expression of nuclear genes for chloroplast proteins of Arabidopsis thaliana.

Excitation imbalances between photosystem I and II generate redox signals in the thylakoid membrane of higher plants which induce acclimatory changes in the structure of the photosynthetic apparatus. They affect the accumulation of reaction center and light-harvesting proteins as well as chlorophylls a and b. In Arabidopsis thaliana the re-adjustment of photosystem stoichiometry is mainly mediated by changes in the number of photosystem I complexes, which are accompanied by corresponding changes in transcripts for plastid reaction center genes. Because chloroplast protein complexes contain also many nuclear encoded components we analyzed the impact of such photosynthetic redox signals on nuclear genes. Light shift experiments combined with application of the electron transport inhibitor 3-(3',4'-dichlorophenyl)-1,1'-dimethyl urea have been performed to induce defined redox signals in the thylakoid membrane. Using DNA macroarrays we assessed the impact of such redox signals on the expression of nuclear genes for chloroplast proteins. In addition, studies on mutants with lesions in cytosolic photoreceptors or in chloroplast-to-nucleus communication indicate that the defective components in the mutants are not essential for the perception and/or transduction of light-induced redox signals. A stable redox state of glutathione suggest that neither glutathione itself nor reactive oxygen species are involved in the observed regulation events pointing to the thylakoid membrane as the main origin of the regulatory pathways. Our data indicate a distinct role of photosynthetic redox signals in the cellular network regulating plant gene expression. These redox signals appear to act independently and/or above of cytosolic photoreceptor or known chloroplast-to-nucleus communication avenues.

Acclimatization↗
PubMed1999

Mitochondrial redox signaling during apoptosis.

The regulatory role of cellular redox state during apoptosis is still controversial. Early redox signaling can transduce divergent upstream signals to mitochondria and initiate apoptosis. On the other hand, release of mitochondrial cytochrome c triggers generation of reactive oxygen species (ROS) and renders apoptotic cells much more oxidized. Although the sequential caspase activation does not have apparent redox-sensitive components, redox signaling provides a separate pathway that is parallel with the caspase cascade. The function of the apoptosis-associated redox change is uncertain. It could provide positive feedback mechanisms, such as activating mitochondrial permeability transition and apoptosis signaling kinase (ASK-1). Since apoptotic cells are designated to be quickly eliminated, the dramatic cellular oxidation could be involved in the final degradation of apoptotic bodies and even the termination of the proteolytic activity after phagocytosis.

Animals↗
PubMedDate not supplied

Glutathione, stress responses, and redox signaling in lung inflammation.

Changes in the ratio of intracellular reduced and disulfide forms of glutathione (GSH/GSSG) can affect signaling pathways that participate in various physiological responses from cell proliferation to gene expression and apoptosis. It is also now known that many proteins have a highly conserved cysteine (sulfhydryl) sequence in their active/regulatory sites, which are primary targets of oxidative modifications and thus important components of redox signaling. However, the mechanism by which oxidants and GSH/protein-cysteine-thiols actually participate in redox signaling still remains to be elucidated. Initial studies involving the role of cysteine in various proteins have revealed that cysteine-SH may mediate redox signaling via reversible or irreversible oxidative modification to Cys-sulfenate or Cys-sulfinate and Cys-sulfonate species, respectively. Oxidative stress possibly via the modification of cysteine residues activates multiple stress kinase pathways and transcription factors nuclear factor-kappaB and activator protein-1, which differentially regulate the genes for proinflammatory cytokines as well as the protective antioxidant genes. Understanding the redox signaling mechanisms for differential gene regulation may allow for the development of novel pharmacological approaches that preferentially up-regulate key antioxidants genes, which, in turn, reduce or resolve inflammation and injury. This forum article features the current knowledge on the role of GSH in redox signaling, particularly the regulation of transcription factors and downstream signaling in lung inflammation.

Animals↗
PubMed2004

Redox signalling: from nitric oxide to oxidized lipids.

Cellular redox signalling is mediated by the post-translational modification of proteins in signal-transduction pathways by ROS/RNS (reactive oxygen species/reactive nitrogen species) or the products derived from their reactions. NO is perhaps the best understood in this regard with two important modifications of proteins known to induce conformational changes leading to modulation of function. The first is the addition of NO to haem groups as shown for soluble guanylate cyclase and the newly discovered NO/cytochrome c oxidase signalling pathway in mitochondria. The second mechanism is through the modification of thiols by NO to form an S-nitrosated species. Other ROS/RNS can also modify signalling proteins although the mechanisms are not as clearly defined. For example, electrophilic lipids, formed as the reaction products of oxidation reactions, orchestrate adaptive responses in the vasculature by reacting with nucleophilic cysteine residues. In modifying signalling proteins ROS/RNS appear to change the overall activity of signalling pathways in a process that we have termed 'redox tone'. In this review, we discuss these different mechanisms of redox cell signalling, and give specific examples of ROS/RNS participation in signal transduction.

Lipid Metabolism↗
PubMed2026

Integrated experimental and bioinformatics analysis reveals ECM-integrin and redox signaling associated with PMMA/NiO nanocomposites for craniofacial applications.

BACKGROUND: Poly(methyl methacrylate) (PMMA) is widely used in dental and craniofacial applications; however, its clinical performance is limited by poor surface wettability, moderate mechanical strength, and restricted biological activity. Integrating nanomaterial engineering with computational biology offers an opportunity to better understand biomaterial-cell interactions and support the rational design of functional biomaterials. METHODS: Nickel oxide (NiO) nanoparticles were synthesized via chemical precipitation and incorporated into PMMA to fabricate nanocomposites. Physicochemical characterization included contact angle measurements, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and Vickers hardness testing. Biocompatibility was evaluated using zebrafish embryo developmental assays. To explore biological processes potentially associated with biomaterial-cell interactions, bioinformatics analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and STRING protein-protein interaction (PPI) network analyses were performed. RESULTS: Incorporation of NiO nanoparticles improved the surface and mechanical properties of PMMA, reducing the contact angle from 105.35° to 90.46° and increasing Vickers hardness compared with unmodified PMMA. Structural and morphological analyses confirmed successful synthesis and homogeneous nanoparticle incorporation. Zebrafish embryo studies demonstrated minimal developmental toxicity, supporting the biocompatibility of the nanocomposite. Bioinformatics analyses identified significant enrichment of pathways related to extracellular matrix organization, cell adhesion, focal adhesion, PI3K-Akt signaling, and oxidative stress regulation. Protein-protein interaction analysis revealed highly interconnected networks associated with ECM-integrin signaling and redox homeostasis, highlighting biological processes potentially associated with biomaterial-cell communication. CONCLUSIONS: PMMA/NiO nanocomposites exhibited improved physicochemical performance and favorable biocompatibility characteristics. The integration of experimental characterization with bioinformatics and network-based analyses provides a systems-level perspective on biomaterial-associated cellular processes and identifies ECM-integrin signaling and oxidative stress-related pathways as candidate biological processes for future experimental validation. These findings support the continued development of PMMA/NiO nanocomposites for oral and craniofacial biomedical applications.

Nanocomposites↗
PubMed2005

Lipid raft clustering and redox signaling platform formation in coronary arterial endothelial cells.

Recent studies have indicated that lipid rafts (LRs) in the cell membrane are clustered in response to different stimuli to form signaling platforms for transmembrane transduction. It remains unknown whether this LR clustering participates in redox signaling in endothelial cells. The present study tested a hypothesis that clustering of LRs on the membrane of coronary endothelial cells produces aggregation and activation of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, thereby forming a redox signaling platform. By confocal microscopic analysis of agonist-stimulated rafts patch formation, we found that several death receptor ligands or apoptotic factors, including tumor necrosis factor alpha, Fas ligand, or endostatin, stimulated the clustering and trafficking of individual LRs on the plasma membrane of coronary endothelial cells. Interestingly, double labeling of a membrane-bound NADPH oxidase subunit, gp91phox, and LRs showed that gp91phox colocalized within the LR patches when endothelial cells were stimulated by Fas ligand. In isolated LR fractions from Fas-stimulated endothelial cells, gp91phox, p47phox (a crucial cytosolic regulatory subunit of NADPH oxidase), and Rac GTPase were markedly increased and blocked by nystatin, a compound that disrupts LRs. These clustered LRs contained high NADPH oxidase activity, which increased in response to Fas stimulation. Functionally, Fas ligand-induced inhibition of endothelium-dependent vasorelaxation was reduced if LRs were disrupted or NADPH oxidase was inhibited. These results suggest that LR clustering occurs in coronary endothelial cells. The formation of redox signaling platforms on the cell membrane mediates transmembrane signaling of death receptors, resulting in endothelial dysfunction.

Animals↗
PubMed2001

Dual involvement of coenzyme Q10 in redox signaling and inhibition of death signaling in the rat heart mitochondria.

Coenzyme Q10 (CoQ) has long been utilized as a cardioprotective agent in various heart diseases. One of the most important mechanisms by which CoQ exerts cardioprotection is aerobic ATP production as a mobile electron carrier in the mitochondrial electron transfer chain. The ability of CoQ to afford myocardial protection is also attributed to its antioxidant property. However, CoQ may also act as a pro-oxidant through the generation of reactive oxygen species. Although excess oxidative stress is known to induce death signaling via cytochrome c release from mitochondria, it is now apparent that a brief exposure to oxidative stress stimulates redox signaling for acquisition of tolerance to oxidative stress. Therefore, we have investigated dual involvement of CoQ in redox signaling generation through enhanced production of reactive oxygen species and death signaling inhibition through antioxidation. Mitochondria were isolated from the rat heart and incubated with CoQ (10 or 100 microM) or its vehicle HCO 60 for 1 h. H2O2 and cytochrome c release from respiring mitochondria were increased by antimycin A (2 microM), an inhibitor of complex III respiratory chain, or by high Ca2+ (10 microM). This enhanced release of H2O2 was associated with an increase in lipid peroxidation as measured with 4-hydroxy-2-nonenal-modified proteins and with large amplitude swelling of mitochondria. CoQ potentiated H2O2 release from antimycin A- or high Ca(2+)-treated mitochondria, but was capable of inhibiting lipid peroxidation and large amplitude swelling, and attenuated cytochrome c release from the mitochondria. In addition, CoQ increased ATP synthesis by mitochondria. These results suggest that CoQ plays dual roles in mitochondrial generation of intracellular signaling. CoQ acts as a pro-oxidant that participates in redox signaling. CoQ also acts as an antioxidant that inhibits permeability transition and cytochrome c release, and increases ATP synthesis, thereby attenuating death signaling toward apoptosis and necrosis.

Adenosine Triphosphate↗
PubMed2005

Redox signaling in colonial hydroids: many pathways for peroxide.

Studies of mitochondrial redox signaling predict that the colonial hydroids Eirene viridula and Podocoryna carnea should respond to manipulations of reactive oxygen species (ROS). Both species encrust surfaces with feeding polyps connected by networks of stolons; P. carnea is more 'sheet-like' with closely spaced polyps and short stolons, while E. viridula is more 'runner-like' with widely spaced polyps and long stolons. Treatment with the chemical antioxidant vitamin C diminishes ROS in mitochondrion-rich epitheliomuscular cells (EMCs) and produces phenotypic effects (sheet-like growth) similar to uncouplers of oxidative phosphorylation. In peripheral stolon tips, treatment with vitamin C triggers a dramatic increase of ROS that is followed by tissue death and stolon regression. The enzymatic anti-oxidant catalase is probably not taken up by the colony but, rather, converts hydrogen peroxide in the medium to water and oxygen. Exogenous catalase does not affect ROS in mitochondrion-rich EMCs, but does increase the amounts of ROS emitted from peripheral stolons, resulting in rapid, runner-like growth. Treatment with exogenous hydrogen peroxide increases ROS levels in stolon tips and results in somewhat faster colony growth. Finally, untreated colonies of E. viridula exhibit higher levels of ROS in stolon tips than untreated colonies of P. carnea. ROS may participate in a number of putative signaling pathways: (1) high levels of ROS may trigger cell and tissue death in peripheral stolon tips; (2) more moderate levels of ROS in stolon tips may trigger outward growth, inhibit branching and, possibly, mediate the redox signaling of mitochondrion-rich EMCs; and (3) ROS may have an extra-colony function, perhaps in suppressing the growth of bacteria.

Analysis of Variance↗
PubMed2001

Redox signalling in chloroplasts and mitochondria: genomic and biochemical evidence for two-component regulatory systems in bioenergetic organelles.

Redox chemistry is central to the primary functions of chloroplasts and mitochondria, that is, to energy conversion in photosynthesis and respiration. However, these bioenergetic organelles always contain very small, specialized genetic systems, relics of their bacterial origin. At huge cost, organellar genomes contain, typically, a mere 0.1% of the genetic information in a eukaryotic cell. There is evidence that chloroplast and mitochondrial genomes encode proteins whose function and biogenesis are particularly tightly governed by electron transfer. We have identified nuclear genes for 'bacterial' histidine sensor kinases and aspartate response regulators that seem to be targeted to chloroplast and mitochondrial membranes. Sequence similarities to cyanobacterial redox signalling components indicate homology and suggest conserved sensory and signalling functions. Two-component redox signalling pathways might be ancient, conserved mechanisms that permit endogenous control over the biogenesis, in situ, of bioenergetic complexes of chloroplasts and mitochondria.

Amino Acid Sequence↗
PubMed1995

Photosynthesis. Regulation by redox signalling.

Photosynthesis is light-driven redox chemistry. Molecular redox signalling, the coupling of gene expression to electron transfer, is now implicated in the adaptation of photosynthesis to variation in light quality and quantity.

Bacterial Proteins↗
PubMed2006

Redox signaling in hypertension.

Diseases such as hypertension, atherosclerosis and diabetes are associated with vascular functional and structural changes including endothelial dysfunction, altered contractility and vascular remodeling. Cellular events underlying these processes involve changes in vascular smooth muscle cell (VSMC) growth, apoptosis/anoikis, cell migration, inflammation, and fibrosis. Many stimuli influence cellular changes, including mechanical forces, such as shear stress, and vasoactive agents, of which angiotensin II (Ang II) appears to be amongst the most important. Ang II mediates many of its pleiotropic vascular effects through NAD(P)H oxidase-derived reactive oxygen species (ROS). Mechanical forces, comprising both unidirectional laminar and oscillatory shear, are increasingly being recognized as important inducers of vascular NO and ROS generation. In general, laminar flow is associated with upregulation of eNOS and NO production and increased expression of antioxidants glutathione peroxidase and superoxide dismutase, thereby promoting a healthy vascular wall and protecting against oxidative vascular injury. On the other hand, oscillatory shear is linked to increased ROS production with consequent oxidative damage, as occurs in hypertension. ROS function as important intracellular and intercellular second messengers to modulate many downstream signaling molecules, such as protein tyrosine phosphatases, protein tyrosine kinases, transcription factors, mitogen-activated protein kinases, and ion channels. Induction of these signaling cascades leads to VSMC growth and migration, expression of pro-inflammatory mediators, and modification of extracellular matrix. In addition, ROS increase intracellular free Ca(2+) concentration, a major determinant of vascular reactivity. ROS influence signaling molecules by altering the intracellular redox state and by oxidative modification of proteins. In physiological conditions, low concentrations of intracellular ROS play an important role in normal redox signaling involved in maintaining vascular function and integrity. Under pathological conditions ROS contribute to vascular dysfunction and remodeling through oxidative damage. The present review describes some of the redox-sensitive signaling pathways that are involved in the functional and structural vascular changes associated with hypertension.

Animals↗