Evidence for a Role of Oxidative Stress in the Carcinogenicity of Ochratoxin A

Thein vitroandin vivoevidence compatible with a role for oxidative stress in OTA carcinogenicity has been collected and described. Several potential oxido-reduction mechanisms have been identified in the past. More recently, the possibility of a reduction of cellular antioxidant defense has been raised as an indirect source of oxidative stress. Consequences resulting from the production of oxidative stress are observed at different levels. First, OTA exposure has been associated with increased levels of oxidative DNA, lipid, and protein damage. Second, various biological processes known to be mobilized under oxidative stress were shown to be altered by OTA. These effects have been observed in bothin vitroandin vivotest systems.In vivo, active doses were often within doses documented to induce renal tumors in rats. In conclusion, the evidence for the induction of an oxidative stress response resulting from OTA exposure can be considered strong. Because the contribution of the oxidative stress response in the development of cancers is well established, a role in OTA carcinogenicity is plausible. Altogether, the data reviewed above support the application of a threshold-based approach to establish safe level of dietary human exposure to OTA.

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Dps and DpsL Mediate SurvivalIn VitroandIn Vivoduring the Prolonged Oxidative Stress Response in Bacteroides fragilis

Journal of Bacteriology ◽

10.1128/jb.00342-15 ◽

2015 ◽

Vol 197 (20) ◽

pp. 3329-3338 ◽

Cited By ~ 12

Author(s):

Michael I. Betteken ◽

Edson R. Rocha ◽

C. Jeffrey Smith

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Peritoneal Cavity ◽

Bacteroides Fragilis ◽

Oxidative Stress Response ◽

Iron Storage ◽

Content Type ◽

Iron Storage Proteins

ABSTRACTBacteroides fragilisis a Gram-negative anaerobe and member of the human intestinal tract microbiome, where it plays many beneficial roles. However, translocation of the organism to the peritoneal cavity can lead to peritonitis, intra-abdominal abscess formation, bacteremia, and sepsis. During translocation,B. fragilisis exposed to increased oxidative stress from the oxygenated tissues of the peritoneal cavity and the immune response. In order to survive,B. fragilismounts a robust oxidative stress response consisting of an acute and a prolonged oxidative stress (POST) response. This report demonstrates that the ability to induce high levels of resistance totert-butyl hydroperoxide (tBOOH) after extended exposure to air can be linked to the POST response. Disk diffusion assays comparing the wild type to a Δdpsmutant and a ΔdpsΔbfrmutant showed greater sensitivity of the mutants to tBOOH after exposure to air, suggesting that Dps and DpsL play a role in the resistance phenotype. Complementation studies withdpsorbfr(encoding DpsL) restored tBOOH resistance, suggesting a role for both of these ferritin-family proteins in the response. Additionally, cultures treated with the iron chelator dipyridyl were not killed by tBOOH, indicating Dps and DpsL function by sequestering iron to prevent cellular damage. Anin vivoanimal model showed that the ΔdpsΔbfrmutant was attenuated, indicating that management of iron is important for survival within the abscess. Together, these data demonstrate a role for Dps and DpsL in the POST response which mediates survivalin vitroandin vivo.IMPORTANCEB. fragilisis the anaerobe most frequently isolated from extraintestinal opportunistic infections, but there is a paucity of information about the factors that allow this organism to survive outside its normal intestinal environment. This report demonstrates that the iron storage proteins Dps and DpsL protect against oxidative stress and that they contribute to survival bothin vitroandin vivo. Additionally, this work demonstrates an important role for the POST response inB. fragilissurvival and provides insight into the complex regulation of this response.

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Lignans Extracted from Eucommia Ulmoides Oliv. Protects Against AGEs-Induced Retinal Endothelial Cell Injury

Cellular Physiology and Biochemistry ◽

10.1159/000447900 ◽

2016 ◽

Vol 39 (5) ◽

pp. 2044-2054 ◽

Cited By ~ 8

Author(s):

Ban Liu ◽

Chao-Peng Li ◽

Wen-Qi Wang ◽

Shu-Guang Song ◽

Xiu-Ming Liu

Keyword(s):

Oxidative Stress ◽

Endothelial Cell ◽

Stress Response ◽

Oxidative Stress Response ◽

Eucommia Ulmoides ◽

Endothelial Cell Function ◽

Retinal Endothelial Cell ◽

Endothelium Damage

Background/Aims: Advanced glycation end products (AGEs) could elicit oxidative stress, trigger and aggravate endothelium damage in several ischemic retinopathies including diabetic retinopathy (DR). The leaves of Eucommia ulmoides O., also referred to as Tu-chung or Du-zhong, have been used for the treatment of hypertension and diabetes, showing great antioxidant activity and anti-glycation activity. Lignans is one of the main bioactive components of Eucommia ulmoides. This study mainly investigated the effect of lignans treatment on AGEs-induced endothelium damage. Methods: MTT assay, Hoechst staining, and calcein-AM/ propidium iodide (PI) staining was conducted to determine the effect of lignans treatment on endothelial cell function in vitro. Retinal trypsin digestion, Evans blue assay, isolectin staining, and western blots were conducted to determine the effect of lignans treatment on retinal microvascular function in vivo. Western blot, protein immunoprecipitation (IP), MTT assays, and enzyme activity assay was conducted to detect the effect of ligans treatment on oxidative stress response. Results: Lignans protected retinal endothelial cell against AGEs-induced injury in vitro and diabetes-induced vascular dysfunction in vivo. Lignans treatment could regulate oxidative stress response in retinal endothelial cell line, retina, and liver. Moreover, we showed that NRF2/HO-1 signaling was critical for lignans-mediated oxidative stress regulation. Conclusion: Lignans treatment could protect against endothelial dysfunction in vivo and in vitro via regulating Nrf2/HO-1 signaling. Lignans might be developed as a promising drug for the treatment of diabetes-induced microvascular dysfunction.

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Gene bb0318 Is Critical for the Oxidative Stress Response and Infectivity of Borrelia burgdorferi

Infection and Immunity ◽

10.1128/iai.00430-16 ◽

2016 ◽

Vol 84 (11) ◽

pp. 3141-3151 ◽

Cited By ~ 7

Author(s):

Adrienne C. Showman ◽

George Aranjuez ◽

Philip P. Adams ◽

Mollie W. Jewett

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Borrelia Burgdorferi ◽

Molecular Mechanisms ◽

De Novo ◽

Oxidative Stress Response ◽

Growth Defect ◽

Content Type

A greater understanding of the molecular mechanisms that Borrelia burgdorferi uses to survive during mammalian infection is critical for the development of novel diagnostic and therapeutic tools to improve the clinical management of Lyme disease. By use of an in vivo expression technology (IVET)-based approach to identify B. burgdorferi genes expressed in vivo , we discovered the bb0318 gene, which is thought to encode the ATPase component of a putative riboflavin ABC transport system. Riboflavin is a critical metabolite enabling all organisms to maintain redox homeostasis. B. burgdorferi appears to lack the metabolic capacity for de novo synthesis of riboflavin and so likely relies on scavenging riboflavin from the host environment. In this study, we sought to investigate the role of bb0318 in B. burgdorferi pathogenesis. No in vitro growth defect was observed for the Δ bb0318 clone. However, the mutant spirochetes displayed reduced levels of survival when exposed to exogenous hydrogen peroxide or murine macrophages. Spirochetes lacking bb0318 were found to have a 100-fold-higher 50% infectious dose than spirochetes containing bb0318 . In addition, at a high inoculum dose, bb0318 was found to be important for effective spirochete dissemination to deep tissues for as long as 3 weeks postinoculation and to be critical for B. burgdorferi infection of mouse hearts. Together, these data implicate bb0318 in the oxidative stress response of B. burgdorferi and indicate the contribution of bb0318 to B. burgdorferi mammalian infectivity.

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Protective effect of Plumericin in inflammatory bowel disease: regulation of inflammatory and oxidative stress response in vitro and in vivo

10.1055/s-0039-3399684 ◽

2019 ◽

Author(s):

SF Rapa ◽

B Waltenberger ◽

R Di Paola ◽

G Autore ◽

S Cuzzocrea ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Bowel Disease ◽

Stress Response ◽

Protective Effect ◽

Bowel Disease ◽

Oxidative Stress Response ◽

Inflammatory Bowel ◽

And Oxidative Stress

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Mitochondrial Sirtuin TcSir2rp3 Affects TcSODA Activity and Oxidative Stress Response in Trypanosoma cruzi

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.773410 ◽

2021 ◽

Vol 11 ◽

Author(s):

Leila dos Santos Moura ◽

Vinícius Santana Nunes ◽

Antoniel A. S. Gomes ◽

Ana Caroline de Castro Nascimento Sousa ◽

Marcos R. M. Fontes ◽

...

Keyword(s):

Oxidative Stress ◽

Superoxide Dismutase ◽

Stress Response ◽

Trypanosoma Cruzi ◽

Conformational Changes ◽

Manganese Superoxide Dismutase ◽

Oxidative Stress Response ◽

Lysine Acetylation

Trypanosoma cruzi faces a variety of environmental scenarios during its life cycle, which include changes in the redox environment that requires a fine regulation of a complex antioxidant arsenal of enzymes. Reversible posttranslational modifications, as lysine acetylation, are a fast and economical way for cells to react to environmental conditions. Recently, we found that the main antioxidant enzymes, including the mitochondrial superoxide dismutase A (TcSODA) are acetylated in T. cruzi, suggesting that protein acetylation could participate in the oxidative stress response in T. cruzi. Therefore, we investigated whether mitochondrial lysine deacetylase TcSir2rp3 was involved in the activity control of TcSODA. We observed an increased resistance to hydrogen peroxide and menadione in parasites overexpressing TcSir2rp3. Increased resistance was also found for benznidazole and nifurtimox, known to induce reactive oxidative and nitrosactive species in the parasite, associated to that a reduction in the ROS levels was observed. To better understand the way TcSir2rp3 could contributes to oxidative stress response, we analyzed the expression of TcSODA in the TcSir2rp3 overexpressing parasites and did not detect any increase in protein levels of this enzyme. However, we found that these parasites presented higher levels of superoxide dismutase activity, and also that TcSir2rp3 and TcSODA interacts in vivo. Knowing that TcSODA is acetylated at lysine residues K44 and K97, and that K97 is located at a similar region in the protein structure as K68 in human manganese superoxide dismutase (MnSOD), responsible for regulating MnSOD activity, we generated mutated versions of TcSODA at K44 and K97 and found that replacing K97 by glutamine, which mimics an acetylated lysine, negatively affects the enzyme activity in vitro. By using molecular dynamics approaches, we revealed that acetylation of K97 induces specific conformational changes in TcSODA with respect to hydrogen-bonding pattern to neighbor residues, suggesting a key participation of this residue to modulate the affinity to O2−. Taken together, our results showed for the first time the involvement of lysine acetylation in the maintenance of homeostatic redox state in trypanosomatids, contributing to the understanding of mechanisms used by T. cruzi to progress during the infection.

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Oxidative stress response of rat testis to model prooxidants in vitro and its modulation

Toxicology in Vitro ◽

10.1016/s0887-2333(02)00092-9 ◽

2002 ◽

Vol 16 (6) ◽

pp. 675-682 ◽

Cited By ~ 12

Author(s):

T Rajesh Kumar ◽

Muralidhara

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Oxidative Stress Response ◽

Rat Testis

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Oxidative stress promotes liver cancer metastasis via a PKA-activated RNF25/ECAD/YAP circuit

10.21203/rs.3.rs-1197819/v1 ◽

2022 ◽

Author(s):

Zhao Huang ◽

Li Zhou ◽

Jiufei Duan ◽

Siyuan Qin ◽

Yu Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Cancer Metastasis ◽

Anoikis Resistance ◽

Antioxidant Genes ◽

Redox Sensor ◽

Stress Signals ◽

Hcc Cells

Abstract Loss of E-cadherin (ECAD), often caused by epigenetic inactivation, is closely associated with tumor metastasis. However, how ECAD is regulated in response to oxidative stress during tumorigenesis is largely unknown. Here we identify RNF25 as a new E3 ligase of ECAD, whose activation by oxidative stress leads to ECAD protein degradation in hepatocellular carcinoma (HCC). Loss of ECAD activates YAP, which in turn promotes the transcription of RNF25, thus forming a positive feedback loop to sustain the ECAD downregulation. YAP activation mitigates oxidative stress in detached HCC cells by upregulating antioxidant genes, protecting detached HCC cells from ferroptosis, resulting in anoikis resistance. Mechanistically, we found that protein kinase A (PKA) senses oxidative stress by redox modification in its β catalytic subunit (PRKACB) at Cys200 and Cys344, which increases its kinase activity towards RNF25 phosphorylation at Ser450, facilitating RNF25-mediated degradation of ECAD. Moreover, RNF25 expression is associated with HCC metastasis and depletion of RNF25 is sufficient to diminish HCC invasion and metastasis in vitro and in vivo. Together, these results identify a dual role of RNF25 as a critical regulator of ECAD protein turnover, promoting both anoikis resistance and metastasis, and PKA is a necessary redox sensor to enable this process. Our study provides mechanistic insight into how tumor cells sense oxidative stress signals to spread while escaping cell death.

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Role of ALADIN in Human Adrenocortical Cells for Oxidative Stress Response and Steroidogenesis

PLoS ONE ◽

10.1371/journal.pone.0124582 ◽

2015 ◽

Vol 10 (4) ◽

pp. e0124582 ◽

Cited By ~ 27

Author(s):

Ramona Jühlen ◽

Jan Idkowiak ◽

Angela E. Taylor ◽

Barbara Kind ◽

Wiebke Arlt ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Oxidative Stress Response ◽

Adrenocortical Cells

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A Protective Role of Paeoniflorin in Fluctuant Hyperglycemia-Induced Vascular Endothelial Injuries through Antioxidative and Anti-Inflammatory Effects and Reduction of PKCβ1

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/5647219 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Jing-Shang Wang ◽

Ye Huang ◽

Shuping Zhang ◽

Hui-Jun Yin ◽

Lei Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Protein Level ◽

Umbilical Vein ◽

Protective Role ◽

Vascular Endothelial ◽

Glucose Levels ◽

Umbilical Vein Endothelial Cells

Hyperglycemia fluctuation is associated with diabetes mellitus (DM) complications when compared to persistent hyperglycemia. Previous studies have shown that paeoniflorin (PF), through its antiapoptosis, anti-inflammation, and antithrombotic properties, effectively protects against cardiovascular and cerebrovascular disease. However, the mechanism underlying the protection from PF against vascular injuries induced by hyperglycemia fluctuations remains poorly understood. Herein, we investigated the potential protective role of PF on human umbilical vein endothelial cells (HUVECs) subjected to intermittent glucose levels in vitro and in DM rats with fluctuating hyperglycemia in vivo. A remarkable increased apoptosis associated with elevated inflammation, increased oxidative stress, and high protein level of PKCβ1 was induced in HUVECs by intermittently changing glucose for 8 days, and PF recovered those detrimental changes. LY333531, a potent PKCβ1 inhibitor, and metformin manifested similar effects. Additionally, in DM rats with fluctuating hyperglycemia, PF protected against vascular damage as what has been observed in vitro. Taken together, PF attenuates the vascular injury induced by fluctuant hyperglycemia through oxidative stress inhibition, inflammatory reaction reduction, and PKCβ1 protein level repression, suggesting its perspective clinical usage.

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