The Combination of PEITC (Phenehyl Isothiocyanate) with a Histone Deacetylase Inhibitor (HDACi) Has Synergistic Antileukemia Activity by Overcoming a Redox-Mediated Resistance Pathway.

Abstract Abstract 1739 Poster Board I-765 Introduction Histone deacetylase inhibitors (HDACI) have limited but well established clinical activity in human leukemia. Results of a phase 1 trial of vorinostat in AML indicate that a gene signature composed mainly of antioxidants was associated with clinical resistance to vorinostat (Blood 2008;111:1060-60). This study suggested that generation of reactive oxygen species (ROS) appears to be a mechanism of action of vorinostat whereas increase of antioxidants may correlate with vorinostat resistance. The aims of this study were to further investigate the underlying molecular mechanisms and test the combination effect of vorinostat and redox modulation agents. Methods and results The parental HL60 and the pan-HDACI resistant HL60/LR were used to compare the redox parameters in this pair of cell lines. Real time PCR and western blot analysis demonstrated that a variety of glutathione related antioxidant defense enzymes were substantially increased in HL60/LR compared to its parental HL60, which is consistent with the clinical findings cited above. Most importantly, Nrf2, a master transcription factor that activates the transcription of cellular defense and antioxidant genes was also upregulated in HL60/LR. Confocal microscopy study showed that vorinostat treatment of HL60 cells caused translocation of Nrf2 from cytosol to nucleus. Furthermore, its downstream antioxidant genes including GST (glutathione S- Transferase), GSR (glutathione reductase), GCLC (glutathione synthase) and SOD (superoxide dismutase) were upregulated, demonstrating that the cellular defense against oxidative stress was induced by vorinostat. Overexpression of Nrf2 in HEK293 cells prevented ROS generation induced by vorinostat. Knock-down of Nrf2 by siRNA in colon cancer cell HCT116 caused increase of ROS production and cytotoxicity induced by vorinostat. These findings further demonstrated the role of Nrf2 in protecting cells from oxidative stress caused by vorinostat. We also observed that vorinostat substantially activated a ROS generating enzyme NADPH Oxidase (NOX) in various AML cell lines including HL60, U937 and ML1. Vorinostat induced ROS in both HL60 and the mitochondrial deficient cell line HL60-C6F. This indicates that NOX is a major source of ROS generation induced by vorinostat. As a result, modulation of antioxidant response may potentiate the cytotoxic activity of vorinostat. In order to modulate cellular redox balance and overcome the resistance to vorinostat, PEITC, a compound known to deplete cellular glutathione was used to test its combination effect with vorinostat. We found that a subtoxic concentration of PEITC (1-2.5 uM) substantially potentiated cytotoxicity of vorinostat in a dose-dependent manner in various AML cell lines, as demonstrated by Annexin-PI assay after 48 hrs and MTT assay after 72 hrs. Treatment with subtoxic concentrations of vorinostat (1.5 uM) and PEITC (1-2.5 uM) for 48 hrs also resulted in synergistic cytotoxicity in primary leukemia cells obtained from AML patient samples as demonstrated by Annexin-PI assay. Parallel results were also obtained with other HDACI such as MGCD0103. Conclusions Our study indicates that NADPH Oxidase is likely a major source of ROS generation induced by vorinostat. Nrf2, a master transcription factor and its downstream antioxidant genes, which protect cells from oxidative stress, contributes to leukemia cellular resistance to vorinostat. Modulation of cellular redox balance such as depletion of glutathione by PEITC significantly potentiates the anti-leukemia activity of vorinostat. Our study provides important information for further development of a mechanism-based combination strategy to maximize the potential of vorinostat and other HDACI and provides an alternative mechanism of the anti-leukemia activity of HDACI. Disclosures No relevant conflicts of interest to declare.

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PERK mediates oxidative stress and adipogenesis in Graves’ orbitopathy pathogenesis

Journal of Molecular Endocrinology ◽

10.1530/jme-21-0057 ◽

2021 ◽

Author(s):

JaeSang Ko ◽

Ji-Young Kim ◽

Min Kyung Chae ◽

Eun Jig Lee ◽

Jin Sook Yoon

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Endoplasmic Reticulum ◽

Transcription Factor ◽

Er Stress ◽

Adipogenic Differentiation ◽

Ros Generation ◽

Mrna Levels ◽

Graves Orbitopathy ◽

Orbital Fibroblasts

We examined endoplasmic reticulum (ER) stress-related gene expression in orbital tissues from patients with Graves’ orbitopathy (GO) and the effects of silencing protein kinase RNA-like endoplasmic reticulum kinase (PERK) in primary orbital fibroblast cultures to demonstrate the therapeutic potential of PERK-modulating agents in GO management. The expression of ER stress related genes in orbital tissue harvested from individuals with or without GO was studied using real-time polymerase chain reaction. The role of PERK in GO pathogenesis was examined through small-interfering RNA (siRNA)-mediated silencing in cultured primary orbital fibroblasts. Intracellular reactive oxygen species (ROS) levels induced in response to cigarette smoke extract (CSE) or hydrogen peroxide were measured using 5-(and 6)-carboxy-20,70-dichlorodihydrofluorescein diacetate staining and flow cytometry. Cells were stained with Oil Red O, and adipogenesis-related transcription factor expression was evaluated through western blotting after adipogenic differentiation. PERK, activating transcription factor 4 (ATF4), and CCAAT-enhancer-binding protein (C/EBP)-homologous protein(CHOP)mRNA levels were significantly higher in GO orbital tissues than in non-GO orbital tissues. PERK silencing inhibited CSE- or hydrogen peroxide-induced ROS generation. After adipogenic differentiation, GO orbital fibroblasts revealed decreased lipid droplets and downregulation of C/EBPα, C/EBPβ, and peroxisome proliferator-activator gamma (PPARγ) in PERK siRNA-transfected cells. The orbital tissues of patients with GO were exposed to chronic ER stress and subsequently exhibited enhanced unfolded protein response (especially through the PERK pathway). PERK silencing reduced oxidative stress and adipogenesis in GO orbital fibroblasts in vitro. Our results imply that PERK-modulating agents can potentially be used to manage GO.

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A standardized extract of Asparagus officinalis stem improves HSP70-mediated redox balance and cell functions in bovine cumulus-granulosa cells

Scientific Reports ◽

10.1038/s41598-021-97632-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Khoi Thieu Ho ◽

Kohei Homma ◽

Jun Takanari ◽

Hanako Bai ◽

Manabu Kawahara ◽

...

Keyword(s):

Cell Function ◽

Redox Balance ◽

Asparagus Officinalis ◽

Hsp70 Expression ◽

Ros Generation ◽

Cellular Redox ◽

Pheochromocytoma Cells ◽

Cell Functions ◽

Progesterone Synthesis ◽

Hsp70 Induction

AbstractHeat shock (HS) protein 70 (HSP70), a well-known HS-induced protein, acts as an intracellular chaperone to protect cells against stress conditions. Although HS induces HSP70 expression to confer stress resistance to cells, HS causes cell toxicity by increasing reactive oxygen species (ROS) levels. Recently, a standardized extract of Asparagus officinalis stem (EAS), produced from the byproduct of asparagus, has been shown to induce HSP70 expression without HS and regulate cellular redox balance in pheochromocytoma cells. However, the effects of EAS on reproductive cell function remain unknown. Here, we investigated the effect of EAS on HSP70 induction and oxidative redox balance in cultured bovine cumulus-granulosa (CG) cells. EAS significantly increased HSP70 expression; however, no effect was observed on HSP27 and HSP90 under non-HS conditions. EAS decreased ROS generation and DNA damage and increased glutathione (GSH) synthesis under both non-HS and HS conditions. Moreover, EAS synergistically increased HSP70 and HSF1 expression and increased progesterone levels in CG cells. Treatment with an HSP70 inhibitor significantly decreased GSH level, increased ROS level, and decreased HSF1, Nrf2, and Keap1 expression in the presence of EAS. Furthermore, EAS significantly increased progesterone synthesis. Thus, EAS improves HSP70-mediated redox balance and cell function in bovine CG cells.

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PICH, an ATP-dependent chromatin remodeling protein, transcriptionally co-regulates oxidative stress response.

10.1101/2021.07.21.453306 ◽

2021 ◽

Author(s):

Anindita Dutta ◽

Apurba Das ◽

Deep Bisht ◽

Vijendra Arya ◽

Rohini Muthuswami

Keyword(s):

Oxidative Stress ◽

Transcription Factor ◽

Transcriptional Regulation ◽

Stress Response ◽

Chromatin Remodeling ◽

Dna Sequences ◽

Target Genes ◽

Antioxidant Response ◽

Oxidative Stress Response ◽

Antioxidant Genes

Cells respond to oxidative stress by elevating the levels of antioxidants, signaling, and transcriptional regulation often implemented by chromatin remodeling proteins. The study presented in this paper shows that the expression of PICH, an ATP-dependent chromatin remodeler, is upregulated during oxidative stress in HeLa cells. We also show that PICH regulates the expression of Nrf2, a transcription factor regulating antioxidant response, both in the absence and presence of oxidative stress. In turn, Nrf2 regulates the expression of PICH in the presence of oxidative stress. Both PICH and Nrf2 together regulate the expression of antioxidant genes and this transcriptional regulation is dependent on the ATPase activity of PICH. In addition, H3K27ac modification also plays a role in activating transcription in the presence of oxidative stress. Co-immunoprecipitation experiments show that PICH and Nrf2 interact with H3K27ac in the presence of oxidative stress. Mechanistically, PICH recognizes ARE sequences present on its target genes and introduces a conformational change to the DNA sequences leading us to hypothesize that PICH regulates transcription by remodeling DNA. PICH ablation leads to reduced expression of Nrf2 and impaired antioxidant response leading to increased ROS content, thus, showing PICH is essential for the cell to respond to oxidative stress.

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Peroxiporins Are Induced Upon Oxidative Stress Insult and Are Associated with Oxidative Stress Resistance in Colon Cancer Cell Lines

Antioxidants ◽

10.3390/antiox10111856 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1856

Author(s):

Ana Čipak Gašparović ◽

Lidija Milković ◽

Claudia Rodrigues ◽

Monika Mlinarić ◽

Graça Soveral

Keyword(s):

Oxidative Stress ◽

Colon Cancer ◽

Transcription Factor ◽

Cell Lines ◽

Stress Resistance ◽

Therapy Resistance ◽

Colon Cancer Cell ◽

Colon Cancer Cell Lines ◽

Intracellular Ros ◽

Ht 29

Oxidative stress can induce genetic instability and change cellular processes, resulting in colorectal cancer. Additionally, adaptation of oxidative defense causes therapy resistance, a major obstacle in successful cancer treatment. Peroxiporins are aquaporin membrane channels that facilitate H2O2 membrane permeation, crucial for regulating cell proliferation and antioxidative defense. Here, we investigated four colon cancer cell lines (Caco-2, HT-29, SW620, and HCT 116) for their sensitivity to H2O2, cellular antioxidative status, and ROS intracellular accumulation after H2O2 treatment. The expression of peroxiporins AQP1, AQP3, and AQP5 and levels of NRF2, the antioxidant transcription factor, and PPARγ, a transcription factor that regulates lipid metabolism, were evaluated before and after oxidative insult. Of the four tested cell lines, HT-29 was the most resistant and showed the highest expression of all tested peroxiporins and the lowest levels of intracellular ROS, without differences in GSH levels, catalase activity, nor NF2 and PPARγ levels. Caco-2 shows high expression of AQP3 and similar resistance as HT-29. These results imply that oxidative stress resistance can be obtained by several mechanisms other than the antioxidant defense system. Regulation of intracellular ROS through modulation of peroxiporin expression may represent an additional strategy to target the therapy resistance of cancer cells.

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Cystine/glutamate antiporter xCT (SLC7A11) facilitates oncogenic RAS transformation by preserving intracellular redox balance

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1821323116 ◽

2019 ◽

Vol 116 (19) ◽

pp. 9433-9442 ◽

Cited By ~ 47

Author(s):

Jonathan K. M. Lim ◽

Alberto Delaidelli ◽

Sean W. Minaker ◽

Hai-Feng Zhang ◽

Milena Colovic ◽

...

Keyword(s):

Oxidative Stress ◽

Transcription Factor ◽

Redox Balance ◽

Gene Encoding ◽

Oncogenic Ras ◽

Opposing Effects ◽

Whole Transcriptome ◽

Intracellular Redox

The RAS family of proto-oncogenes are among the most commonly mutated genes in human cancers and predict poor clinical outcome. Several mechanisms underlying oncogenic RAS transformation are well documented, including constitutive signaling through the RAF-MEK-ERK proproliferative pathway as well as the PI3K-AKT prosurvival pathway. Notably, control of redox balance has also been proposed to contribute to RAS transformation. However, how homeostasis between reactive oxygen species (ROS) and antioxidants, which have opposing effects in the cell, ultimately influence RAS-mediated transformation and tumor progression is still a matter of debate and the mechanisms involved have not been fully elucidated. Here, we show that oncogenic KRAS protects fibroblasts from oxidative stress by enhancing intracellular GSH levels. Using a whole transcriptome approach, we discovered that this is attributable to transcriptional up-regulation of xCT, the gene encoding the cystine/glutamate antiporter. This is in line with the function of xCT, which mediates the uptake of cystine, a precursor for GSH biosynthesis. Moreover, our results reveal that the ETS-1 transcription factor downstream of the RAS-RAF-MEK-ERK signaling cascade directly transactivates the xCT promoter in synergy with the ATF4 endoplasmic reticulum stress-associated transcription factor. Strikingly, xCT was found to be essential for oncogenic KRAS-mediated transformation in vitro and in vivo by mitigating oxidative stress, as knockdown of xCT strongly impaired growth of tumor xenografts established from KRAS-transformed cells. Overall, this study uncovers a mechanism by which oncogenic RAS preserves intracellular redox balance and identifies an unexpected role for xCT in supporting RAS-induced transformation and tumorigenicity.

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ARNT Mediates Chemotherapy Resistance by Modulating the Response to Oxidative Stress in AML Cells.

Blood ◽

10.1182/blood.v114.22.2737.2737 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2737-2737

Author(s):

Richard A. Wells ◽

Chunhong Gu ◽

Joelle dela Paz

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Cell Lines ◽

Akt Signaling ◽

Mrna Levels ◽

Antioxidant Genes ◽

Protein Levels ◽

Exogenous Expression ◽

Induction Of Apoptosis ◽

Induced Apoptosis

Abstract Abstract 2737 Poster Board II-713 Background Although patients with acute myelogenous leukaemia (AML) typically respond well to initial therapy, with over 75% of patients achieving complete remission, in the great majority the disease ultimately relapses. This is thought to be due to the inherent resistance of leukaemia stem cells to the effects of chemotherapy. While some mechanisms of chemoresistance, e.g. TP53 mutation and upregulation of P-glycoprotein expression, have been well characterized, this phenomenon remains incompletely understood and is a significant barrier to improving patient outcomes. Methods and results The thiazolidindione drug troglitazone (TG) induces apoptosis in AML cells via generation of intracellular reactive oxygen species (ROS), but the degree of sensitivity to TG is highly heterogeneous among AML cell lines. We studied expression of the transcription factor ARNT (aryl hydrocarbon nuclear translocator) in TG-sensitive and TG-resistant AML cell lines following TG treatment. In HL-60 cells, which are highly sensitive to induction of apoptosis by TG, ARNT mRNA levels remained constant following TG treatment and ARNT protein levels markedly decreased, while in U937 cells, which are TG resistant, ARNT mRNA levels increased and ARNT protein levels remained constant. We then tested the effect of exogenous expression of ARNT on the sensitivity of HL-60 cells to TG-induced apoptosis. HL-60 cells transduced with a retrovirus expressing ARNT became TG-resistant. Exogenous expression of ARNT also conferred resistance to induction of apoptosis by hydrogen peroxide, daunorubicin and etoposide. The cellular response to oxidative stress is governed by intracellular signaling pathways and through a transcriptional response through which expression of antioxidant genes is coordinated. HL-60 cells expressing ARNT had striking constitutive activation of AKT signaling, and treatment of these cells with a specific inhibitor of AKT signaling reversed their resistance to TG-induced apoptosis. The activation of AKT signaling by ARNT appears to be mediated by downregulation of expression of PP2A and alpha4, two key negative regulators of AKT phosphorylation. In addition, ARNT-transduced HL-60 cells showed increased expression of Nrf2, a key transcriptional regulator of the antioxidant response, and its target genes SOD2 and CAT. Conclusions The response to oxidative stress is heterogeneous in AML cells lines, and varies with expression of ARNT. ARNT activates expression of Nrf2, which stimulates expression of antioxidant genes resulting in an augmented adaptive response to ROS. Unexpectedly, ARNT also activates AKT signaling by repressing expression of the regulatory phosphatases PP2A and alpha4. These activities of ARNT result in increased resistance to the induction of apoptosis by TG, hydrogen peroxide, and chemotherapy. ARNT may play an important role in chemoresistance in and may be useful as a predictive or prognostic biomarker. Disclosures: No relevant conflicts of interest to declare.

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Antcin C fromAntrodia cinnamomeaProtects Liver Cells Against Free Radical-Induced Oxidative Stress and ApoptosisIn VitroandIn Vivothrough Nrf2-Dependent Mechanism

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/296082 ◽

2013 ◽

Vol 2013 ◽

pp. 1-17 ◽

Cited By ~ 26

Author(s):

M. Gokila Vani ◽

K. J. Senthil Kumar ◽

Jiunn-Wang Liao ◽

Shih-Chang Chien ◽

Jeng-Leun Mau ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Transcriptional Activation ◽

Liver Cells ◽

Ros Generation ◽

Antioxidant Genes ◽

Pi3k Activation ◽

Mice Liver ◽

Induced Apoptosis

In this study, we investigated the cytoprotective effects of antcin C, a steroid-like compound isolated from Antrodia cinnamaomea against AAPH-induced oxidative stress and apoptosis in human hepatic HepG2 cells. Pretreatment with antcin C significantly protects hepatic cells from AAPH-induced cell death through the inhibition of ROS generation. Furthermore, AAPH-induced lipid peroxidation, ALT/AST secretion and GSH depletion was significantly inhibited by antcin C. The antioxidant potential of antcin C was correlated with induction of antioxidant genes including, HO-1, NQO-1,γ-GCLC, and SODviatranscriptional activation of Nrf2. The Nrf2 activation by antcin C is mediated by JNK1/2 and PI3K activation, whereas pharmacologic inhibition of JNK1/2 and PI3K abolished antcin C-induced Nrf2 activity. In addition, AAPH-induced apoptosis was significantly inhibited by antcin C through the down-regulation of pro-apoptotic factors including, Bax, cytochrome c, capase 9, -4, -12, -3, and PARP.In vivostudies also show that antcin C significantly protected mice liver from AAPH-induced hepatic injury as evidenced by reduction in hepatic enzymes in circulation. Further, immunocytochemistry analyses showed that antcin C significantly increased HO-1 and Nrf2 expression in mice liver tissues. These results strongly suggest that antcin C could protect liver cells from oxidative stress and cell deathviaNrf2/ARE activation.

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Redox Potential of Antioxidants in Cancer Progression and Prevention

Antioxidants ◽

10.3390/antiox9111156 ◽

2020 ◽

Vol 9 (11) ◽

pp. 1156

Author(s):

Sajan George ◽

Heidi Abrahamse

Keyword(s):

Oxidative Stress ◽

Cancer Progression ◽

Natural Antioxidants ◽

Redox Balance ◽

Redox Status ◽

Enzyme Activation ◽

Metabolic Reprogramming ◽

Cellular Functions ◽

Cellular Redox ◽

The Right

The benevolent and detrimental effects of antioxidants are much debated in clinical trials and cancer research. Several antioxidant enzymes and molecules are overexpressed in oxidative stress conditions that can damage cellular proteins, lipids, and DNA. Natural antioxidants remove excess free radical intermediates by reducing hydrogen donors or quenching singlet oxygen and delaying oxidative reactions in actively growing cancer cells. These reducing agents have the potential to hinder cancer progression only when administered at the right proportions along with chemo-/radiotherapies. Antioxidants and enzymes affect signal transduction and energy metabolism pathways for the maintenance of cellular redox status. A decline in antioxidant capacity arising from genetic mutations may increase the mitochondrial flux of free radicals resulting in misfiring of cellular signalling pathways. Often, a metabolic reprogramming arising from these mutations in metabolic enzymes leads to the overproduction of so called ’oncometabolites’ in a state of ‘pseudohypoxia’. This can inactivate several of the intracellular molecules involved in epigenetic and redox regulations, thereby increasing oxidative stress giving rise to growth advantages for cancerous cells. Undeniably, these are cell-type and Reactive Oxygen Species (ROS) specific, which is manifested as changes in the enzyme activation, differences in gene expression, cellular functions as well as cell death mechanisms. Photodynamic therapy (PDT) using light-activated photosensitizing molecules that can regulate cellular redox balance in accordance with the changes in endogenous ROS production is a solution for many of these challenges in cancer therapy.

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Flavonoids Activation of the Transcription Factor Nrf2 as a Hypothesis Approach for the Prevention and Modulation of SARS-CoV-2 Infection Severity

Antioxidants ◽

10.3390/antiox9080659 ◽

2020 ◽

Vol 9 (8) ◽

pp. 659 ◽

Cited By ~ 6

Author(s):

Patricia Mendonca ◽

Karam F. A. Soliman

Keyword(s):

Oxidative Stress ◽

Transcription Factor ◽

Viral Entry ◽

Viral Infections ◽

Ros Generation ◽

Respiratory Epithelial Cells ◽

Angiotensin Converting Enzyme 2 ◽

Impaired Immune Response ◽

Respiratory Epithelial ◽

And Oxidative Stress

The Nrf2-Keap1-ARE pathway is the principal regulator of antioxidant and phase II detoxification genes. Its activation increases the expression of antioxidant and cytoprotective proteins, protecting cells against infections. Nrf2 modulates virus-induced oxidative stress, ROS generation, and disease pathogenesis, which are vital in the viral life cycle. During respiratory viral infections, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an inflammatory process, and oxidative stress of the epithelium lining cells activate the transcription factor Nrf2, which protects cells from oxidative stress and inflammation. Nrf2 reduces angiotensin-converting enzyme 2 (ACE2) receptors expression in respiratory epithelial cells. SARS-CoV2 has a high affinity for ACE2 that works as receptors for coronavirus surface spike glycoprotein, facilitating viral entry. Disease severity may also be modulated by pre-existing conditions, such as impaired immune response, obesity, and age, where decreased level of Nrf2 is a common feature. Consequently, Nrf2 activators may increase Nrf2 levels and enhance antiviral mediators’ expression, which could initiate an “antiviral state”, priming cells against viral infection. Therefore, this hypothesis paper describes the use of flavonoid supplements combined with vitamin D3 to activate Nrf2, which may be a potential target to prevent and/or decrease SARS-CoV-2 infection severity, reducing oxidative stress and inflammation, enhancing innate immunity, and downregulating ACE2 receptors.

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The rhodanese RhdA helps Azotobacter vinelandii in maintaining cellular redox balance

Biological Chemistry ◽

10.1515/bc.2010.073 ◽

2010 ◽

Vol 391 (7) ◽

Cited By ~ 12

Author(s):

William Remelli ◽

Angelo Cereda ◽

Jutta Papenbrock ◽

Fabio Forlani ◽

Silvia Pagani

Keyword(s):

Oxidative Stress ◽

Stress Condition ◽

Azotobacter Vinelandii ◽

Redox Balance ◽

Cysteine Residue ◽

Structural Peculiarity ◽

Cellular Redox ◽

Catalytic Cysteine ◽

Transcript Profiles

AbstractThe tandem domain rhodanese-homology protein RhdA ofAzotobacter vinelandiishows an active-site loop structure that confers structural peculiarity in the environment of its catalytic cysteine residue. Thein vivoeffects of the lack of RhdA were investigated using anA. vinelandiimutant strain (MV474) in which therhdAgene was disrupted by deletion. Here, by combining analytical measurements and transcript profiles, we show that deletion of therhdAgene generates an oxidative stress condition to whichA. vinelandiiresponds by activating defensive mechanisms. In conditions of growth in the presence of the superoxide generator phenazine methosulfate, a stressor-dependent induction ofrhdAgene expression was observed, thus highlighting that RhdA is important forA. vinelandiito sustain oxidative stress. The potential of RhdA to buffer general levels of oxidants inA. vinelandiicells via redox reactions involving its cysteine thiol is discussed.

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