The effect of cigarette smoking on endothelial damage and atherosclerosis development – modeled and analyzed using Petri nets

Abstract Atherosclerosis as one of the crucial causes of cardiovascular diseases (CVD) is the leading reason of death worldwide. One of the contributing factors to this phenomenon is endothelial dysfunction, which is associated with the impact of various agents and their interactions. Tobacco smoke is one of the well known factors here. For better understanding of its significance a model of its impact on atherosclerotic plaque formation has been proposed. The model contains selected aspects of the influence of tobacco smoke, dual function of nitric oxide (NO) (influence of various mechanisms on NO bioavailability), oxidative stress which promotes low density lipoproteins oxidation, macrophages significance and other mechanisms leading to an aggravation of the endothelial disturbances. The model has been built using Petri nets theory and the analysis has been based on t-invariants. This approach allowed to confirm the important role of inflammation and oxidative stress in atherosclerosis development and moreover it has shown the considerable influence of the cigarette smoke.

Download Full-text

Antioxidants Promote Intestinal Tumor Progression in Mice

Antioxidants ◽

10.3390/antiox10020241 ◽

2021 ◽

Vol 10 (2) ◽

pp. 241

Author(s):

Zhiyuan V. Zou ◽

Kristell Le Gal ◽

Ahmed E. El Zowalaty ◽

Lara E. Pehlivanoglu ◽

Viktor Garellick ◽

...

Keyword(s):

Oxidative Stress ◽

Colorectal Cancer ◽

Tumor Progression ◽

Human Subjects ◽

Plasma Concentrations ◽

Intestinal Tumor ◽

Adenomatous Polyposis ◽

Intestinal Tumors ◽

The Impact

Dietary antioxidants and supplements are widely used to protect against cancer, even though it is now clear that antioxidants can promote tumor progression by helping cancer cells to overcome barriers of oxidative stress. Although recent studies have, in great detail, explored the role of antioxidants in lung and skin tumors driven by RAS and RAF mutations, little is known about the impact of antioxidant supplementation on other cancers, including Wnt-driven tumors originating from the gut. Here, we show that supplementation with the antioxidants N-acetylcysteine (NAC) and vitamin E promotes intestinal tumor progression in the ApcMin mouse model for familial adenomatous polyposis, a hereditary form of colorectal cancer, driven by Wnt signaling. Both antioxidants increased tumor size in early neoplasias and tumor grades in more advanced lesions without any impact on tumor initiation. Importantly, NAC treatment accelerated tumor progression at plasma concentrations comparable to those obtained in human subjects after prescription doses of the drug. These results demonstrate that antioxidants play an important role in the progression of intestinal tumors, which may have implications for patients with or predisposed to colorectal cancer.

Download Full-text

The Impact of Oxidative Stress on Testicular Function and the Role of Antioxidants in Improving it: A Review

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2017/23927.9886 ◽

2017 ◽

Cited By ~ 16

Author(s):

Nematollah Asadi

Keyword(s):

Oxidative Stress ◽

Testicular Function ◽

The Impact

Download Full-text

PmtA Regulates Pyocyanin Expression and Biofilm Formation in Pseudomonas aeruginosa

Frontiers in Microbiology ◽

10.3389/fmicb.2021.789765 ◽

2021 ◽

Vol 12 ◽

Author(s):

Amy V. Thees ◽

Kathryn M. Pietrosimone ◽

Clare K. Melchiorre ◽

Jeremiah N. Marden ◽

Joerg Graf ◽

...

Keyword(s):

Oxidative Stress ◽

Pseudomonas Aeruginosa ◽

Metal Binding ◽

Biofilm Formation ◽

Binding Capacity ◽

Opportunistic Pathogen ◽

Small Molecular Weight ◽

Heavy Metal Binding ◽

The Impact

The opportunistic pathogen Pseudomonas aeruginosa expresses a small molecular weight, cysteine-rich protein (PmtA), identified as a metallothionein (MT) protein family member. The MT family proteins have been well-characterized in eukaryotes as essential for zinc and copper homeostasis, protection against oxidative stress, and the ability to modify a variety of immune activities. Bacterial MTs share sequence homology, antioxidant chemistry, and heavy metal-binding capacity with eukaryotic MTs, however, the impact of bacterial MTs on virulence and infection have not been well-studied. In the present study, we investigated the role of PmtA in P. aeruginosa PAO1 using a PmtA-deficient strain (ΔpmtA). Here we demonstrated the virulence factor, pyocyanin, relies on the expression of PmtA. We showed that PmtA may be protective against oxidative stress, as an alternative antioxidant, glutathione, can rescue pyocyanin expression. Furthermore, the expression of phzM, which encodes a pyocyanin precursor enzyme, was decreased in the ΔpmtA mutant during early stationary phase. Upregulated pmtA expression was previously detected in confluent biofilms, which are essential for chronic infection, and we observed that the ΔpmtA mutant was disrupted for biofilm formation. As biofilms also modulate antibiotic susceptibility, we examined the ΔpmtA mutant susceptibility to antibiotics and found that the ΔpmtA mutant is more susceptible to cefepime and ciprofloxacin than the wild-type strain. Finally, we observed that the deletion of pmtA results in decreased virulence in a waxworm model. Taken together, our results support the conclusion that PmtA is necessary for the full virulence of P. aeruginosa and may represent a potential target for therapeutic intervention.

Download Full-text

Circulating Leukocytes and Oxidative Stress in Cardiovascular Diseases: A State of the Art

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/2650429 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Speranza Rubattu ◽

Maurizio Forte ◽

Salvatore Raffa

Keyword(s):

Oxidative Stress ◽

Cardiovascular Diseases ◽

Stress Level ◽

Mononuclear Cells ◽

Pathological Condition ◽

Clinical Manifestations ◽

Therapeutic Interventions ◽

Oxidative Stress Level ◽

The Impact

Increased oxidative stress from both mitochondrial and cytosolic sources contributes to the development and the progression of cardiovascular diseases (CVDs), and it is a target of therapeutic interventions. The numerous efforts made over the last decades in order to develop tools able to monitor the oxidative stress level in patients affected by CVDs rely on the need to gain information on the disease state. However, this goal has not been satisfactorily accomplished until now. Among others, the isolation of circulating leukocytes to measure their oxidant level offers a valid, noninvasive challenge that has been tested in few pathological contexts, including hypertension, atherosclerosis and its clinical manifestations, and heart failure. Since leukocytes circulate in the blood stream, it is expected that they might reflect quite closely both systemic and cardiovascular oxidative stress and provide useful information on the pathological condition. The results of the studies discussed in the present review article are promising. They highlight the importance of measuring oxidative stress level in circulating mononuclear cells in different CVDs with a consistent correlation between degree of oxidative stress and severity of CVD and of its complications. Importantly, they also point to a double role of leukocytes, both as a marker of disease condition and as a direct contributor to disease progression. Finally, they show that the oxidative stress level of leukocytes reflects the impact of therapeutic interventions. It is likely that the isolation of leukocytes and the measurement of oxidative stress, once adequately developed, may represent an eligible tool for both research and clinical purposes to monitor the role of oxidative stress on the promotion and progression of CVDs, as well as the impact of therapies.

Download Full-text

Oxidative Stress and Adipocyte Biology: Focus on the Role of AGEs

Oxidative Medicine and Cellular Longevity ◽

10.1155/2015/534873 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 31

Author(s):

Florence Boyer ◽

Jennifer Baraka Vidot ◽

Alexis Guerin Dubourg ◽

Philippe Rondeau ◽

M. Faadiel Essop ◽

...

Keyword(s):

Oxidative Stress ◽

Adipose Tissue ◽

Advanced Glycation Endproducts ◽

Glycated Albumin ◽

Major Health Problem ◽

Glycation Endproducts ◽

Diabetes Progression ◽

The Impact ◽

Pathologic Processes

Diabetes is a major health problem that is usually associated with obesity, together with hyperglycemia and increased advanced glycation endproducts (AGEs) formation. Elevated AGEs elicit severe downstream consequences via their binding to receptors of AGEs (RAGE). This includes oxidative stress and oxidative modifications of biological compounds together with heightened inflammation. For example, albumin (major circulating protein) undergoes increased glycoxidation with diabetes and may represent an important biomarker for monitoring diabetic pathophysiology. Despite the central role of adipose tissue in many physiologic/pathologic processes, recognition of the effects of greater AGEs formation in this tissue is quite recent within the obesity/diabetes context. This review provides a brief background of AGEs formation and adipose tissue biology and thereafter discusses the impact of AGEs-adipocyte interactions in pathology progression. Novel data are included showing how AGEs (especially glycated albumin) may be involved in hyperglycemia-induced oxidative damage in adipocytes and its potential links to diabetes progression.

Download Full-text

MAPKs and NF-κB differentially regulate cytokine expression in the diaphragm in response to resistive breathing: the role of oxidative stress

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00376.2010 ◽

2011 ◽

Vol 300 (5) ◽

pp. R1152-R1162 ◽

Cited By ~ 39

Author(s):

Ioanna Sigala ◽

Panayiotis Zacharatos ◽

Dimitris Toumpanakis ◽

Tatiana Michailidou ◽

Olga Noussia ◽

...

Keyword(s):

Oxidative Stress ◽

Cytokine Expression ◽

Regulatory Control ◽

Protein Levels ◽

Cytokine Induction ◽

Resistive Breathing ◽

Tnf Α ◽

The Impact ◽

To Receive

Inspiratory resistive breathing (IRB) induces cytokine expression in the diaphragm. The mechanism of this cytokine induction remains elusive. The roles of MAPKs and NF-κB and the impact of oxidative stress in IRB-induced cytokine upregulation in the diaphragm were studied. Wistar rats were subjected to IRB (50% of maximal inspiratory pressure) via a two-way nonrebreathing valve for 1, 3, or 6 h. Additional groups of rats subjected to IRB for 6 h were randomly assigned to receive either solvent or N-acetyl-cysteine (NAC) or inhibitors of NF-κB (BAY-11–7082), ERK1/2 (PD98059), and P38 MAPK (SB203580) to study the effect of oxidative stress, NF-κB, and MAPKs in IRB-induced cytokine upregulation in the diaphragm. Quietly breathing animals served as controls. IRB upregulated cytokine (IL-6, TNF-α, IL-10, IL-2, IL-1β) protein levels in the diaphragm and resulted in increased activation of MAPKs (P38, ERK1/2) and NF-κB. Inhibition of NF-κB and ERK1/2 blunted the upregulation of all cytokines except that of IL-6, which was further increased. P38 inhibition attenuated all cytokine (including IL-6) upregulation. Both P38 and ERK1/2 inhibition decreased NF-κB/p65 subunit phosphorylation. NAC pretreatment blunted IRB-induced cytokine upregulation in the diaphragm and resulted in decreased ERK1/2, P38, and NF-κB/p65 phosphorylation. In conclusion, IRB-induced cytokine upregulation in the diaphragm is under the regulatory control of MAPKs and NF-κB. IL-6 is regulated differently from all other cytokines through a P38-dependent and NF-κB independent pathway. Oxidative stress is a stimulus for IRB-induced cytokine upregulation in the diaphragm.

Download Full-text

Connexin Gap Junctions and Hemichannels in Modulating Lens Redox Homeostasis and Oxidative Stress in Cataractogenesis

Antioxidants ◽

10.3390/antiox10091374 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1374

Author(s):

Yumeng Quan ◽

Yu Du ◽

Yuxin Tong ◽

Sumin Gu ◽

Jean X. Jiang

Keyword(s):

Oxidative Stress ◽

Gap Junction ◽

Redox Homeostasis ◽

Cell Communication ◽

Underlying Mechanism ◽

Post Translational Modifications ◽

Gap Junction Channels ◽

Mediate Cell ◽

The Impact

The lens is continuously exposed to oxidative stress insults, such as ultraviolet radiation and other oxidative factors, during the aging process. The lens possesses powerful oxidative stress defense systems to maintain its redox homeostasis, one of which employs connexin channels. Connexins are a family of proteins that form: (1) Hemichannels that mediate the communication between the intracellular and extracellular environments, and (2) gap junction channels that mediate cell-cell communication between adjacent cells. The avascular lens transports nutrition and metabolites through an extensive network of connexin channels, which allows the passage of small molecules, including antioxidants and oxidized wastes. Oxidative stress-induced post-translational modifications of connexins, in turn, regulates gap junction and hemichannel permeability. Recent evidence suggests that dysfunction of connexins gap junction channels and hemichannels may induce cataract formation through impaired redox homeostasis. Here, we review the recent advances in the knowledge of connexin channels in lens redox homeostasis and their response to cataract-related oxidative stress by discussing two major aspects: (1) The role of lens connexins and channels in oxidative stress and cataractogenesis, and (2) the impact and underlying mechanism of oxidative stress in regulating connexin channels.

Download Full-text

Ozone-Induced Oxidative Stress, Neutrophilic Airway Inflammation, and Glucocorticoid Resistance in Asthma

Frontiers in Immunology ◽

10.3389/fimmu.2021.631092 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chioma Enweasor ◽

Cameron H. Flayer ◽

Angela Haczku

Keyword(s):

Oxidative Stress ◽

Airway Inflammation ◽

Γδ T Cells ◽

Air Pollutant ◽

Glucocorticoid Resistance ◽

Primary Data ◽

Alveolar Type ◽

Underlying Mechanisms ◽

The Impact

Despite recent advances in using biologicals that target Th2 pathways, glucocorticoids form the mainstay of asthma treatment. Asthma morbidity and mortality remain high due to the wide variability of treatment responsiveness and complex clinical phenotypes driven by distinct underlying mechanisms. Emerging evidence suggests that inhalation of the toxic air pollutant, ozone, worsens asthma by impairing glucocorticoid responsiveness. This review discusses the role of oxidative stress in glucocorticoid resistance in asthma. The underlying mechanisms point to a central role of oxidative stress pathways. The primary data source for this review consisted of peer-reviewed publications on the impact of ozone on airway inflammation and glucocorticoid responsiveness indexed in PubMed. Our main search strategy focused on cross-referencing “asthma and glucocorticoid resistance” against “ozone, oxidative stress, alarmins, innate lymphoid, NK and γδ T cells, dendritic cells and alveolar type II epithelial cells, glucocorticoid receptor and transcription factors”. Recent work was placed in the context from articles in the last 10 years and older seminal research papers and comprehensive reviews. We excluded papers that did not focus on respiratory injury in the setting of oxidative stress. The pathways discussed here have however wide clinical implications to pathologies associated with inflammation and oxidative stress and in which glucocorticoid treatment is essential.

Download Full-text

Role of Silicon in Mediating Salt Tolerance in Plants: A Review

Plants ◽

10.3390/plants8060147 ◽

2019 ◽

Vol 8 (6) ◽

pp. 147 ◽

Cited By ~ 26

Author(s):

Yong-Xing Zhu ◽

Hai-Jun Gong ◽

Jun-Liang Yin

Keyword(s):

Oxidative Stress ◽

Salt Stress ◽

Osmotic Stress ◽

Stress Responses ◽

Polyamine Metabolism ◽

Research Areas ◽

Aquaporin Gene ◽

Ion Imbalance ◽

The Impact

Salt stress is a major threat for plant growth worldwide. The regulatory mechanisms of silicon in alleviating salt stress have been widely studied using physiological, molecular genetics, and genomic approaches. Recently, progresses have been made in elucidating the alleviative effects of silicon in salt-induced osmotic stress, Na toxicity, and oxidative stress. In this review, we highlight recent development on the impact of silicon application on salt stress responses. Emphasis will be given to the following aspects. (1) Silicon transporters have been experimentally identified in different plant species and their structure feature could be an important molecular basis for silicon permeability. (2) Silicon could mediate salt-induced ion imbalance by (i) regulating Na+ uptake, transport, and distribution and (ii) regulating polyamine levels. (3) Si-mediated upregulation of aquaporin gene expression and osmotic adjustment play important roles in alleviating salinity-induced osmotic stress. (4) Silicon application direct/indirectly mitigates oxidative stress via regulating the antioxidant defense and polyamine metabolism. (5) Omics studies reveal that silicon could regulate plants’ response to salt stress by modulating the expression of various genes including transcription factors and hormone-related genes. Finally, research areas that require further investigation to provide a deeper understanding of the role of silicon in plants are highlighted.

Download Full-text