A novel cis-element that is responsive to oxidative stress regulates three antioxidant defense genes in rice

All organisms have defense systems against oxidative stress that include multiple genes of antioxidant defense. These genes are induced by reactive oxygen species under condition of oxidative stress. In this study, we found that a 28-bp motif is conserved on the promoter regions of three antioxidant defense genes in rice (Oryza sativa): cytosolic superoxide dismutase (sodCc1), cytosolic thioredoxin (trxh), and glutaredoxin (grx). We demonstrated that the 28-bp sequence acts as a cis-element responsive to oxidative stress by transient expression assay and designated it as CORE (coordinate regulatory element for antioxidant defense). The CORE was activated by methyl viologen treatment and induced a 3.1-fold increase in expression of the reporter gene, but it did not respond to hydrogen peroxide. The expressions of the sodCc1, trxh, and grx genes were coordinately induced by methyl viologen, suggesting that multiple genes involved in antioxidant defense are controlled by a common regulatory mechanism via CORE. Application of the mitogen-activated protein kinase kinase inhibitor caused the constitutive induction of the sodCc1, trxh, and grx genes and the activation of CORE without methyl viologen treatment. These results indicate that a mitogen-activated protein kinase cascade is involved in the gene regulation mediated by CORE.     

Phosphosite-specific regulation of the oxidative-stress response of Paracoccidioides brasiliensis: a shotgun phosphoproteomic analysis

Paracoccidioides brasiliensis, a thermally dimorphic fungus, is the causative agent of paracoccidioidomycosis, a systemic mycosis that is widespread in Latin America. This fungus is a facultative intracellular pathogen able to survive and replicate inside non-activated macrophages. Therefore, the survival of P. brasiliensis inside the host depends on the ability to adapt to oxidative stress induced by immune cells, especially alveolar macrophages. For several years, reactive oxygen species (ROS) were only associated with pathological processes. Currently, a plethora of roles for ROS in cell signaling have emerged. We have previously reported that low ROS concentrations cause cell proliferation in the human pathogenic fungus P. brasiliensis. In the present report, we investigated the influence of phosphorylation events in that process. Using a mass spectrometry-based approach, we mapped 440 phosphorylation sites in 230 P. brasiliensis proteins and showed that phosphorylation at different sites determines fungal responses to oxidative stress, which are regulated by phosphatases and kinases activities. Furthermore, we present additional evidence for a functional two-component signal transduction system in P. brasiliensis. These findings will help us to understand the phosphorylation events involved in the oxidative stress response.     

Reactive oxygen species and the strategy of the antioxidant defense in fungi: a review

The level of reactive oxygen species (ROS) in the cell regulates the growth and differentiation of the fungal organism. This review considers the pathways of generation of the primary ROS and the defense methods used by fungi and yeasts against them as well as the involvement of thiol compounds in the antioxidant defense of the fungal cell. It is demonstrated that the adaptation of fungi to oxidative stress is tightly connected with the redox-dependent changes in the activities of antioxidant defense components.     

Reactive oxygen species and the strategy of antioxidant defense in fungi: A review

The level of reactive oxygen species (ROS) in the cell regulates the growth and differentiation of the fungal organism. This review considers the pathways of generation of the primary ROS and the defense methods used by fungi and yeasts against them as well as the involvement of thiol compounds in the antioxidant defense of the fungal cell. It is demonstrated that the adaptation of fungi to oxidative stress is tightly connected with the redox-dependent changes in the activities of antioxidant defense components.     

Antioxidant responses to oxidant-mediated lung diseases

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated throughout the human body. Enzymatic and nonenzymatic antioxidants detoxify ROS and RNS and minimize damage to biomolecules. An imbalance between the production of ROS and RNS and antioxidant capacity leads to a state of "oxidative stress" that contributes to the pathogenesis of a number of human diseases by damaging lipids, protein, and DNA. In general, lung diseases are related to inflammatory processes that generate increased ROS and RNS. The susceptibility of the lung to oxidative injury depends largely on its ability to upregulate protective ROS and RNS scavenging systems. Unfortunately, the primary intracellular antioxidants are expressed at low levels in the human lung and are not acutely induced when exposed to oxidative stresses such as cigarette smoke and hyperoxia. However, the response of extracellular antioxidant enzymes, the critical primary defense against exogenous oxidative stress, increases rapidly and in proportion to oxidative stress. In this paper, we review how antioxidants in the lung respond to oxidative stress in several lung diseases and focus on the mechanisms that upregulate extracellular glutathione peroxidase.     

Skin cells and tissue are capable of using l-ergothioneine as an integral component of their antioxidant defense system

The cellular defense system against harmful levels of reactive oxygen species consists of antioxidant enzymatic activities and small nonenzymatic molecules. l-Ergothioneine has long been recognized as a potent and stable low-molecular-weight antioxidant that humans consume with diet and that accumulates in cells normally subjected to high levels of oxidative stress. As l-ergothioneine is plasma membrane-impermeative, its protective function is restricted to cells that express the l-ergothioneine-specific receptor/transporter OCTN1. Here we report for the first time that both as resident skin cells and in culture, epidermal keratinocytes synthesize OCTN1, which enables them to internalize and accumulate l-ergothioneine. This accumulation confers upon the cells an increased antioxidant potential. Consequently, it reduces the levels of reactive oxygen species and DNA, protein, and lipid damage in keratinocytes subjected to solar-simulating UV oxidative stress. Our results suggest that l-ergothioneine not only prevents oxidative damage but also may enable DNA repair in the UV-irradiated cells. The diminished oxidative damage to cellular constituents limits the apoptotic response and results in increased cell viability. The cells' ability to take up, accumulate, and utilize the potent antioxidant l-ergothioneine positions this naturally occurring amino acid and its receptor/transporter as an integral part of the antioxidative defense system of the skin.     

The response of Paracoccidioides spp. to nitrosative stress

Paracoccidioidomycosis (PCM) is an endemic disease in Latin America caused by species belonging to the genus Paracoccidioides. During infection, immune cells present a variety of defense mechanisms against pathogens. One of these defensive strategies is the production and release of nitric oxide (NO) and S-nitroso thiols (e.g., S-nitrosoglutathione, GSNO), which produce reactive nitrogen species (RNS). This results in damage to DNA and membranes, inhibition of respiration and inactivation of cellular enzymes. In response to nitrosative stress, human pathogenic fungi possess defense mechanisms to prevent the adverse effects of NO, which helps them survive during initial contact with the host immune system. To understand how Paracoccidioides spp. respond to nitrosative stress, we conducted this study to identify genes and proteins that might contribute to this response. The results of proteomic analysis demonstrated that nitrosative stress induced a reduction in the expression of proteins related to the mitochondrial electron transport chain. This hypothesis was supported by the reduced mitochondrial activity observed in the presence of GSNO. Additionally, lipids and branched chain amino acid metabolism enzymes were altered. The role played by enzymes acting in oxidative stress in the RNS response was remarkable. This interface among enzymes acting in both stress responses was confirmed by using a RNA approach to silence the ccp gene in Paracoccidioides. It was observed that mutants with low expression of the ccp gene were more sensitive to nitrosative stress.     

Selective Up-regulation of Human Selenoproteins in Response to Oxidative Stress

Selenocysteine is inserted into selenoproteins via the translational recoding of a UGA codon, normally used as a stop signal. This process depends on the nature of the selenocysteine insertion sequence element located in the 3′ UTR of selenoprotein mRNAs, selenium bioavailability, and, possibly, exogenous stimuli. To further understand the function and regulation of selenoproteins in antioxidant defense and redox homeostasis, we investigated how oxidative stress influences selenoprotein expression as a function of different selenium concentrations. We found that selenium supplementation of the culture media, which resulted in a hierarchical up-regulation of selenoproteins, protected HEK293 cells from reactive oxygen species formation. Furthermore, in response to oxidative stress, we identified a selective up-regulation of several selenoproteins involved in antioxidant defense (Gpx1, Gpx4, TR1, SelS, SelK, and Sps2). Interestingly, the response was more efficient when selenium was limiting. Although a modest change in mRNA levels was noted, we identified a novel translational control mechanism stimulated by oxidative stress that is characterized by up-regulation of UGA-selenocysteine recoding efficiency and relocalization of SBP2, selenocysteine-specific elongation factor, and L30 recoding factors from the cytoplasm to the nucleus.     

Is alpha-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity

The chemical reduction and oxidation (redox) properties of alpha-lipoic acid (LA) suggest that it may have potent antioxidant potential. A significant number of studies now show that LA and its reduced form, dihydrolipoic acid (DHLA), directly scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) species and protect cells against a host of insults where oxidative stress is part of the underlying etiology. However, owing to its limited and transient accumulation in tissues following oral intake, the efficacy of nonprotein-bound LA to function as a physiological antioxidant has been questioned. Herein, we review the evidence that the micronutrient functions of LA may be more as an effector of important cellular stress response pathways that ultimately influence endogenous cellular antioxidant levels and reduce proinflammatory mechanisms. This would promote a sustained improvement in cellular resistance to pathologies where oxidative stress is involved, which would not be forthcoming if LA solely acted as a transient ROS scavenger.     

Differential efficiency of two strains of the arbuscular mycorrhizal fungus Rhizophagus irregularis on olive (Olea europaea) plants under two water regimes

The water regime affects a wide variety of physiological and biochemical processes in plants including an increased production of reactive oxygen species (ROS) capable of causing oxidative damage to proteins, DNA and lipids. Arbuscular mycorrhizal fungi (AMF) colonize a wide range of plant species though the ability of different AMF species to promote host growth or contribute to plant water deficit resistance varies. The first phase of olive tree cultivation takes place in a nursery where plants usually suffer stress by drying. Currently, olive production systems do not use of AMF to counteract this problem. To study the colonization strategies of two AMF strains and their efficiency with respect to growth and their effect on enzymatic activities, we inoculated them individually and co-inoculated then on olive plants under nursery growing conditions. The results showed the benefits generated by these fungi in terms of growth and survival rate. Co-inoculation, particularly, improved growth and reduced the damage due to water stress, partly as a result of the activation of the antioxidant defenses in the olive plant host.