scholarly journals Cellular Mechanisms of Oxidative Stress and Action in Melanoma

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Mario Venza ◽  
Maria Visalli ◽  
Concetta Beninati ◽  
Giuseppe Valerio De Gaetano ◽  
Diana Teti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Methylation ◽  
Methylation Pattern ◽  
The Body ◽  
Current Evidence ◽  
Cellular Mechanisms ◽  
Melanoma Diagnosis ◽  
Life Threatening ◽  
Induced Changes ◽  
The Impact

Most melanomas occur on the skin, but a small percentage of these life-threatening cancers affect other parts of the body, such as the eye and mucous membranes, including the mouth. Given that most melanomas are caused by ultraviolet radiation (UV) exposure, close attention has been paid to the impact of oxidative stress on these tumors. The possibility that key epigenetic enzymes cannot act on a DNA altered by oxidative stress has opened new perspectives. Therefore, much attention has been paid to the alteration of DNA methylation by oxidative stress. We review the current evidence about (i) the role of oxidative stress in melanoma initiation and progression; (ii) the mechanisms by which ROS influence the DNA methylation pattern of transformed melanocytes; (iii) the transformative potential of oxidative stress-induced changes in global and/or local gene methylation and expression; (iv) the employment of this epimutation as a biomarker for melanoma diagnosis, prognosis, and drug resistance evaluation; (v) the impact of this new knowledge in clinical practice for melanoma treatment.

Epigenetic modifications in acute lymphoblastic leukemia: From cellular mechanisms to therapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Ezzatollah Fathi ◽  
Raheleh Farahzadi ◽  
Soheila Montazersaheb ◽  
Yasin Bagheri
Keyword(s):  
Dna Methylation ◽  
Acute Lymphoblastic Leukemia ◽  
Histone Modification ◽  
Epigenetic Modification ◽  
Lymphoblastic Leukemia ◽  
Underlying Mechanism ◽  
Methylation Pattern ◽  
Epigenetic Alterations ◽  
Cellular Mechanisms ◽  
Novel Treatments

Background:: Epigenetic modification pattern is considered as a characteristic feature in blood malignancies. Modifications in the DNA methylation modulators are recurrent in lymphoma and leukemia, so that, the distinct methylation pattern defines different types of leukemia. Generally, the role of epigenetics is less understood and most investigations are focused on genetic abnormalities and cytogenic studies to develop novel treatments for patients with hematologic disorders. Recently, understanding the underlying mechanism of acute lymphoblastic leukemia (ALL), especially epigenetic altera-tions as a driving force in the development of ALL opens a new era of investigation for developing promising strategy, be-yond available conventional therapy. Objective:: This review will focus on a better understanding of the epigenetic mechanisms in cancer development and pro-gression, with an emphasis on epigenetic alterations in ALL including, DNA methylation, histone modification, and mi-croRNA alterations. Other topics that will be discussed include the use of epigenetic alterations as a promising therapeutic target in order to develop novel well-suited approaches against ALL. Conclusion:: According to the literature review, leukemogenesis of ALL is extensively influenced by epigenetic modifica-tions, particularly DNA hyper-methylation, histone modification, and miRNA alteration.

A Mechanistic Motor-Clutch Model That Explains Cell Shape Dynamics to Cyclic Stretch

2022 ◽  
Author(s):  
Benjamin W. Scandling ◽  
Jia Gou ◽  
Jessica Thomas ◽  
Jacqueline Xuan ◽  
Chuan Xue ◽  
...  
Keyword(s):  
Computational Model ◽  
Computational Models ◽  
The Body ◽  
Cyclic Stretch ◽  
Substrate Stiffness ◽  
Cell Alignment ◽  
Cellular Mechanisms ◽  
Actin Bundles ◽  
The Impact

Many cells in the body experience cyclic mechanical loading, which can impact cellular processes and morphology. In vitro studies often report that cells reorient in response to cyclic stretch of their substrate. To explore cellular mechanisms involved in this reorientation, a computational model was developed by utilizing the previous computational models of the actin-myosin-integrin motor-clutch system developed by others. The computational model predicts that under most conditions, actin bundles align perpendicular to the direction of applied cyclic stretch, but under specific conditions, such as low substrate stiffness, actin bundles align parallel to the direction of stretch. The model also predicts that stretch frequency impacts the rate of reorientation, and that proper myosin function is critical in the reorientation response. These computational predictions are consistent with reports from the literature and new experimental results presented here. The model suggests that the impact of different stretching conditions (stretch type, amplitude, frequency, substrate stiffness, etc.) on the direction of cell alignment can largely be understood by considering their impact on cell-substrate detachment events, specifically whether detachment occurs during stretching or relaxing of the substrate.

DNA methylation versus gene expression

Development ◽  
1984 ◽  
Vol 83 (Supplement) ◽  
pp. 31-40
Author(s):  
Adrian P. Bird
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cell Division ◽  
Methylation Pattern ◽  
Current Evidence ◽  
Evolutionary Perspective ◽  
Cell Type ◽  
Versus Gene ◽  
Daughter Cells ◽  
The Relationship

Vertebrate DNA is methylated at a high proportion of cytosine residues in the sequence CpG, and it has been suggested that the distribution of methylated and non-methylated CpGs in a given cell type influences the pattern of gene expression in those cells. Since a DNA methylation pattern is normally transmitted faithfully to daughter cells via cell division, this idea suggests an origin for stable, clonally inherited patterns of gene expression. This article discusses some of the current evidence for a relationship between DNA methylation and gene expression. Although the evidence is incomplete, it appears already that the relationship is variable: transcription of some genes is repressed by the presence of 5-methylcytosine at certain CpGs, and may be controlled by methylation, while transcription of other genes is indifferent to methylation. In attempting to explain this variability it is helpful to adopt an evolutionary perspective.

scholarly journals A four-DNA methylation biomarker is a superior predictor of survival of patients with cutaneous melanoma

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Wenna Guo ◽  
Liucun Zhu ◽  
Rui Zhu ◽  
Qihan Chen ◽  
Qiang Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cutaneous Melanoma ◽  
Cox Regression ◽  
Predictive Accuracy ◽  
Immune Checkpoint Blockade ◽  
Melanoma Diagnosis ◽  
Kaplan Meier ◽  
Genome Wide ◽  
Life Threatening ◽  
Distinct Separation

Cutaneous melanoma (CM) is a life-threatening form of skin cancer. Prognostic biomarkers can reliably stratify patients at initial melanoma diagnosis according to risk, and may inform clinical decisions. Here, we performed a retrospective, cohort-based study analyzing genome-wide DNA methylation of 461 patients with CM from the TCGA database. Cox regression analyses were conducted to establish a four-DNA methylation signature that was significantly associated with the overall survival (OS) of patients with CM, and that was validated in an independent cohort. Corresponding Kaplan–Meier analysis displayed a distinct separation in OS. The ROC analysis confirmed that the predictive signature performed well. Notably, this signature exhibited much higher predictive accuracy in comparison with known biomarkers. This signature was significantly correlated with immune checkpoint blockade (ICB) immunotherapy-related signatures, and may have potential as a guide for measures of responsiveness to ICB immunotherapy.

Brain stem oxidative stress and its associated signaling in the regulation of sympathetic vasomotor tone

2012 ◽  
Vol 113 (12) ◽  
pp. 1921-1928 ◽  
Author(s):  
Samuel H. H. Chan ◽  
Julie Y. H. Chan
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Brain Stem ◽  
Ventrolateral Medulla ◽  
Future Research ◽  
Vasomotor Tone ◽  
Cellular Mechanisms ◽  
Neurogenic Hypertension ◽  
The Impact ◽  
Sympathetic Vasomotor Tone

There is now compelling evidence from studies in humans and animals that overexcitation of the sympathetic nervous system plays an important role in the pathogenesis of cardiovascular diseases. An excellent example is neurogenic hypertension, in which central sympathetic overactivation is involved in the development, staging, and progression of the disease, and one of the underlying mechanisms involves oxidative stress in key brain stem sites that are engaged in the regulation of sympathetic vasomotor tone. Using the rostral ventrolateral medulla (RVLM) and nucleus tractus solitarii (NTS) as two illustrative brain stem neural substrates, this article provides an overview of the impact of reactive oxygen species and antioxidants on RVLM and NTS in the pathogenesis of neurogenic hypertension. This is followed by a discussion of the redox-sensitive signaling pathways, including several kinases, ion channels, and transcription factors that underpin the augmentation in sympathetic vasomotor tone. In addition, the emerging view that brain stem oxidative stress is also causally related to a reduction in sympathetic vasomotor tone and hypotension during brain stem death, methamphetamine intoxication, and temporal lobe status epilepticus will be presented, along with the causal contribution of the oxidant peroxynitrite formed by a reaction between nitric oxide synthase II (NOS II)-derived nitric oxide and superoxide. Also discussed as a reasonable future research direction is dissection of the cellular mechanisms and signaling cascades that may underlie the contributory role of nitric oxide generated by different NOS isoforms in the differential effects of oxidative stress in the RVLM or NTS on sympathetic vasomotor tone.

The Impact of Morin, a Natural Flavonoid, on Cyclophosphamide-Induced Changes in the Oxidative Stress Parameters in Rat Livers

2014 ◽  
Vol 23 (4) ◽  
pp. 505-509 ◽  
Author(s):  
Anna Merwid-Ląd ◽  
Małgorzata Trocha ◽  
Ewa Chlebda-Sieragowska ◽  
Tomasz Sozański ◽  
Marta Szandruk ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Stress Parameters ◽  
Induced Changes ◽  
The Impact ◽  
Rat Livers ◽  
Stress Parameters

The Impact of Exercise on DNA Methylation of Genes Associated with Type 2 Diabetes and Obesity in Human Adipose Tissue

2014 ◽  
Vol 10 (01) ◽  
pp. 64 ◽  
Author(s):  
Tina Rönn ◽  
Charlotte Ling ◽  
◽  
Keyword(s):  
Type 2 Diabetes ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Short Review ◽  
Methylation Pattern ◽  
Cellular Level ◽  
Genetic And Environmental Factors ◽  
The Impact

It is well established that exercise promotes health, and reduces people’s risks for developing type 2 diabetes and becoming obese. But just how exercise performs this, at a cellular level, and what molecular and physiologic steps are involved and in what order, are still not fully understood. Metabolic disorders are often influenced by interactions between genetic and environmental factors. One possible explanation for how the environment may influence the genome is through epigenetic mechanisms–that is–chemical modifications to the DNA itself. Epigenetic factors include, for example, DNA methylation, histone modifications, and different RNA-mediated processes, which all have the ability to bind to DNA or affect the chromatin structure and thereby change how specific genes are interpreted and expressed. In this short review, we focus on describing how exercise influences the genome-wide DNA methylation pattern, including candidate genes for obesity and type 2 diabetes, in human adipose tissue.

scholarly journals Inhibition of Oxidative Stress in Brain During Rat Adjuvant Arthritis by Carnosine, Trolox and Novel Trolox-Carnosine

2015 ◽  
pp. S489-S496
Author(s):  
S. PONIŠT ◽  
L. SLOVÁK ◽  
V. KUNCÍROVÁ ◽  
T. FEDOROVA ◽  
A. LOGVINENKO ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Weight Reduction ◽  
Adjuvant Arthritis ◽  
The Body ◽  
Protein Carbonyls ◽  
Therapeutic Effects ◽  
Arthritic Score ◽  
Markers Of Inflammation ◽  
Rat Adjuvant Arthritis ◽  
The Impact

Carnosine (CARN) is an anti-glycating agent able to quench superoxide, and to neutralize 4-hydroxynonenal. Trolox-carnosine (CARN-T) was synthesized because of its resistance against degradation and to improve CARN antioxidant capacity. We evaluated the impact of trolox (TRO), CARN and its derivative CARN-T on oxidative stress (OS) in brain during rat adjuvant arthritis (AA). The experiments were done on healthy, control arthritic and arthritic animals with administration of CARN 150 mg/kg b.w., TRO 41 mg/kg b.w. and CARN-T 75 mg/kg b.w. in a daily dose during 28 days. Antioxidants did not affect the body weight on day 14, but on day 28 TRO enhanced the weight reduction. On day 14 and 28 CARN-T and TRO reduced arthritic score. IL-1beta, MCP-1 and MMP-9 were measured in plasma on day 14. MCP-1 was decreased by CARN-T and TRO. All antioxidants reduced IL-1beta and MMP-9 levels. Malondialdehyde, 4-hydroxynonenal and protein carbonyls were increased in brain. CARN, CARN-T and TRO prevented higher lipid and protein oxidation in brain. CARN and CARN-T caused no weight reduction like TRO that has an advantage in inflammatory arthritis. Moreover the antioxidants administered had a similar therapeutic effects on arthritic score, markers of inflammation in plasma and OS in brain.

scholarly journals Inflammatory and oxidative status in European captive black rhinoceroses: a link with Iron Overload Disorder?

2020 ◽  
Author(s):  
Hanae Pouillevet ◽  
Nicolas Soetart ◽  
Delphine Boucher ◽  
Rudy Wedlarski ◽  
Laetitia Jaillardon
Keyword(s):  
Oxidative Stress ◽  
Iron Overload ◽  
Serum Iron ◽  
Iron Status ◽  
The Body ◽  
Stress Markers ◽  
Oxidative Markers ◽  
Inflammatory Status ◽  
The Impact ◽  
And Oxidative Stress

AbstractIron Overload Disorder (IOD) is a syndrome developed by captive browsing rhinoceroses like black rhinoceroses (Diceros bicornis) in which hemosiderosis settles in vital organs while free iron accumulates in the body, potentially predisposing to various secondary diseases. Captive grazing species like white rhinoceroses (Ceratotherium simum) do not seem to be affected. The pro-oxidant and pro-inflammatory properties of iron, associated with the poor antioxidant capacities of black rhinoceroses, could enhance high levels of inflammation and oxidative stress leading to rapid ageing and promoting diseases. In this prospective study, 15 black (BR) and 29 white rhinoceroses (WR) originating from 22 European zoos were blood-sampled and compared for their iron status (serum iron), liver/muscle biochemical parameters (AST, GGT, cholesterol), inflammatory status (total proteins, protein electrophoresis) and oxidative stress markers (SOD, GPX, dROMs). Results showed higher serum iron and liver enzyme levels in black rhinoceroses (P<0.01), as well as higher GPX (P<0.05) and dROM (P<0.01) levels. The albumin/globulin ratio was lower in black rhinoceroses (P<0.05) due to higher α2-globulin levels (P<0.001). The present study suggests a higher inflammatory and oxidative profile in captive BR than in WR, possibly in relation to iron status. This could be either a consequence or a cause of iron accumulation, potentially explaining rapid ageing and various diseases. Further investigations are needed to assess the prognostic value of the inflammatory and oxidative markers in captive black rhinoceroses, particularly for evaluating the impact of reduced-iron and antioxidant-supplemented diets.

scholarly journals Oxidative Stress and Inflammation Induced by Waterpipe Tobacco Smoking Despite Possible Protective Effects of Exercise Training: A Review of the Literature

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 777 ◽  
Author(s):  
Behzad Taati ◽  
Hamid Arazi ◽  
Katsuhiko Suzuki
Keyword(s):  
Oxidative Stress ◽  
Exercise Training ◽  
Tobacco Smoking ◽  
Relaxation Method ◽  
The Body ◽  
Protective Effects ◽  
Respiratory Problems ◽  
Risk Of Mortality ◽  
Waterpipe Tobacco Smoking ◽  
The Impact

The prevalence of waterpipe tobacco smoking (WTS), which is also known as ghalyan, shisha or hookah, is increasing rapidly around the world, especially among youth. Growing interest in this form of tobacco smoking can be traced, in part, to the use of flavored tobacco products, social acceptability as a safer option than cigarettes, and its consideration as a relaxation method or entertainment. However, there is a well-established association between WTS and oxidative stress that causes irreversible chronic pathological conditions such as cardiovascular and respiratory problems, as well as different types of cancers, and thus increases the risk of mortality. Clearly, induction of inflammation status through increased reactive oxygen species (ROS), which in turn leads to oxidative stress and harm to lipids, DNA, and proteins, is the most plausible mechanism to explain the potential harmful effects of WTS. Unlike WTS, well-designed exercise training programs increase ROS to the extent that it is beneficial to the body. In this study, we aimed to review available evidence on the impact of exercise training on oxidative stress and inflammation status. We also summarize the effect of acute and chronic WTS on different exercise capacities.

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