scholarly journals Impact of Oxidative Stress in Fetal Programming

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Loren P. Thompson ◽  
Yazan Al-Hasan
Keyword(s):  
Oxidative Stress ◽  
Organ Dysfunction ◽  
Fetal Programming ◽  
Target Genes ◽  
Therapeutic Strategies ◽  
Epigenetic Mechanisms ◽  
Adult Disease ◽  
Specific Target ◽  
Increased Risk

Intrauterine stress induces increased risk of adult disease through fetal programming mechanisms. Oxidative stress can be generated by several conditions, such as, prenatal hypoxia, maternal under- and overnutrition, and excessive glucocorticoid exposure. The role of oxidant molecules as signaling factors in fetal programming via epigenetic mechanisms is discussed. By linking oxidative stress with dysregulation of specific target genes, we may be able to develop therapeutic strategies that protect against organ dysfunction in the programmed offspring.

scholarly journals Role of NADPH Oxidase in Metabolic Disease-Related Renal Injury: An Update

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Cheng Wan ◽  
Hua Su ◽  
Chun Zhang
Keyword(s):  
Oxidative Stress ◽  
Metabolic Disease ◽  
Nadph Oxidase ◽  
Renal Injury ◽  
Mesangial Cells ◽  
Therapeutic Strategies ◽  
Metabolic Factors ◽  
Glomerular Diseases ◽  
Increased Risk

Metabolic syndrome has been linked to an increased risk of chronic kidney disease. The underlying pathogenesis of metabolic disease-related renal injury remains obscure. Accumulating evidence has shown that NADPH oxidase is a major source of intrarenal oxidative stress and is upregulated by metabolic factors leading to overproduction of ROS in podocytes, endothelial cells, and mesangial cells in glomeruli, which is closely associated with the initiation and progression of glomerular diseases. This review focuses on the role of NADPH oxidase-induced oxidative stress in the pathogenesis of metabolic disease-related renal injury. Understanding of the mechanism may help find potential therapeutic strategies.

scholarly journals Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

2021 ◽  
Vol 22 (3) ◽  
pp. 1296
Author(s):  
Yue Ruan ◽  
Subao Jiang ◽  
Adrian Gericke
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Therapeutic Strategies ◽  
Vision Impairment ◽  
Age Related Macular Degeneration ◽  
Oxygen Species ◽  
Age Related

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

scholarly journals The Role of the FOXO1/β2-AR/p-NF-κB p65 Pathway in the Development of Endometrial Stromal Cells in Pregnant Mice under Restraint Stress

2021 ◽  
Vol 22 (3) ◽  
pp. 1478
Author(s):  
Jiayin Lu ◽  
Yaoxing Chen ◽  
Zixu Wang ◽  
Jing Cao ◽  
Yulan Dong
Keyword(s):  
Oxidative Stress ◽  
Stromal Cells ◽  
Restraint Stress ◽  
Target Genes ◽  
Mrna Levels ◽  
Endometrial Stromal Cells ◽  
Protein Levels ◽  
Pregnant Mice

Restraint stress causes various maternal diseases during pregnancy. β2-Adrenergic receptor (β2-AR) and Forkhead transcription factor class O 1 (FOXO1) are critical factors not only in stress, but also in reproduction. However, the role of FOXO1 in restraint stress, causing changes in the β2-AR pathway in pregnant mice, has been unclear. The aim of this research was to investigate the β2-AR pathway of restraint stress and its impact on the oxidative stress of the maternal uterus. In the study, maternal mice were treated with restraint stress by being restrained in a transparent and ventilated device before sacrifice on Pregnancy Day 5 (P5), Pregnancy Day 10 (P10), Pregnancy Day 15 (P15), and Pregnancy Day 20 (P20) as well as on Non-Pregnancy Day 5 (NP5). Restraint stress augmented blood corticosterone (CORT), norepinephrine (NE), and blood glucose levels, while oestradiol (E2) levels decreased. Moreover, restraint stress increased the mRNA levels of the FOXO family, β2-AR, and even the protein levels of FOXO1 and β2-AR in the uterus and ovaries. Furthermore, restraint stress increased uterine oxidative stress level. In vitro, the protein levels of FOXO1 were also obviously increased when β2-AR was activated in endometrial stromal cells (ESCs). In addition, phosphorylated-nuclear factor kappa-B p65 (p-NF-κB p65) and its target genes decreased significantly when FOXO1 was inhibited. Overall, it can be said that the β2-AR/FOXO1/p-NF-κB p65 pathway was activated when pregnant mice were under restraint stress. This study provides a scientific basis for the origin of psychological stress in pregnant women.

scholarly journals miR-21 is upregulated, promoting fibrosis and blocking G2/M in irradiated rat cardiac fibroblasts

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10502
Author(s):  
Huan Guo ◽  
Xinke Zhao ◽  
Haixiang Su ◽  
Chengxu Ma ◽  
Kai Liu ◽  
...  
Keyword(s):  
Myocardial Fibrosis ◽  
Target Genes ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Differentially Expressed Gene ◽  
Stem Loop ◽  
Cardiac Morbidity ◽  
Increased Risk ◽  
And Function

Background Radiation exposure of the thorax is associated with a greatly increased risk of cardiac morbidity and mortality even after several decades of advancement in the field. Although many studies have demonstrated the damaging influence of ionizing radiation on cardiac fibroblast (CF) structure and function, myocardial fibrosis, the molecular mechanism behind this damage is not well understood. miR-21, a small microRNA, promotes the activation of CFs, leading to cardiac fibrosis. miR-21 is overexpressed after irradiation; however, the relationship between increased miR-21 and myocardial fibrosis after irradiation is unclear. This study was conducted to investigate gene expression after radiation-induced CF damage and the role of miR-21 in this process in rats. Methods We sequenced irradiated rat CFs and performed weighted correlation network analysis (WGCNA) combined with differentially expressed gene (DEG) analysis to observe the effect on the expression profile of CF genes after radiation. Results DEG analysis showed that the degree of gene changes increased with the radiation dose. WGCNA revealed three module eigengenes (MEs) associated with 8.5-Gy-radiation—the Yellow, Brown, Blue modules. The three module eigengenes were related to apoptosis, G2/M phase, and cell death and S phase, respectively. By blocking with the cardiac fibrosis miRNA miR-21, we found that miR-21 was associated with G2/M blockade in the cell cycle and was mainly involved in regulating extracellular matrix-related genes, including Grem1, Clu, Gdf15, Ccl7, and Cxcl1. Stem-loop quantitative real-time PCR was performed to verify the expression of these genes. Five genes showed higher expression after 8.5 Gy-radiation in CFs. The target genes of miR-21 predicted online were Gdf15 and Rsad2, which showed much higher expression after treatment with antagomir-miR-21 in 8.5-Gy-irradiated CFs. Thus, miR-21 may play the role of fibrosis and G2/M blockade in regulating Grem1, Clu, Gdf15, Ccl7, Cxcl1, and Rsad2 post-irradiation.

scholarly journals New Insights into Molecular Oncogenesis and Therapy of Uveal Melanoma

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 694 ◽  
Author(s):  
Sara Silvia Violanti ◽  
Ilaria Bononi ◽  
Carla Enrica Gallenga ◽  
Fernanda Martini ◽  
Mauro Tognon ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Target Genes ◽  
Therapeutic Strategies ◽  
Biomedical Sciences ◽  
Therapeutic Approaches ◽  
Common Cancer ◽  
Multistep Process ◽  
Systemic Adjuvant Therapy ◽  
Novel Therapeutic

Uveal melanoma (UM), which is the most common cancer of the eye, was investigated in recent years by many teams in the field of biomedical sciences and eye clinicians. New knowledge was acquired on molecular pathways found to be dysregulated during the multistep process of oncogenesis, whereas novel therapeutic approaches gave significant results in the clinical applications. Uveal melanoma-affected patients greatly benefited from recent advances of the research in this eye cancer. Tumour biology, genetics, epigenetics and immunology contributed significantly in elucidating the role of different genes and related pathways during uveal melanoma onset/progression and UM treatments. Indeed, these investigations allowed identification of new target genes and to develop new therapeutic strategies/compounds to cure this aggressive melanoma of the eye. Unfortunately, the advances reported in the treatment of cutaneous melanoma have not produced analogous benefits in metastatic uveal melanoma. Nowadays, no systemic adjuvant therapy has been shown to improve overall survival or reduce the risk of metastasis. However, the increasing knowledge of this disease, and the encouraging results seen in clinical trials, offer promise for future effective therapies. Herein, different pathways/genes involved in uveal melanoma onset/progression were taken into consideration, together with novel therapeutic approaches.

scholarly journals Melatonin reduces oxidative damage in mouse granulosa cells via restraining JNK-dependent autophagy

Reproduction ◽  
2018 ◽  
Vol 155 (3) ◽  
pp. 307-319 ◽  
Author(s):  
Yan Cao ◽  
Ming Shen ◽  
Yi Jiang ◽  
Shao-chen Sun ◽  
Honglin Liu
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Mammalian Cells ◽  
Therapeutic Strategies ◽  
Oxygen Species ◽  
Protective Effects ◽  
Follicular Atresia ◽  
Direct Role ◽  
Jnk Pathway

Oxidative stress-induced granulosa cell (GCs) injury is believed to be a common trigger for follicular atresia. Emerging evidence indicates that excessive autophagy occurs in mammalian cells with oxidative damage. N-acetyl-5-methoxytrypamine (melatonin) has been shown to prevent GCs from oxidative injury, although the exact mechanism remains to be elucidated. Here, we first demonstrated that the suppression of autophagy through the JNK/BCL-2/BECN1 signaling is engaged in melatonin-mediated GCs protection against oxidative damage. Melatonin inhibited the loss of GCs viability, formation of GFP-MAP1LC3B puncta, accumulation of MAP1LC3B-II blots, degradation of SQSTM1 and the expression of BECN1, which was correlated with impaired activation of JNK during oxidative stress. On the other hand, blocking of autophagy and/or JNK also reduced the level of H2O2-induced GCs death, but failed to further restore GCs viability in the presence of melatonin. Particularly, the suppression of autophagy provided no additional protective effects when GCs were pretreated with JNK inhibitor and/or melatonin. Importantly, we found that the enhanced interaction between BCL-2 and BECN1 might be a responsive mechanism for autophagy suppression via the melatonin/JNK pathway. Moreover, blocking the downstream antioxidant system of melatonin using specific inhibitors further confirmed a direct role of melatonin/JNK/autophagy axis in preserving GCs survival without scavenging reactive oxygen species (ROS). Taken together, our findings uncover a novel function of melatonin in preventing GCs from oxidative damage by targeting JNK-mediated autophagy, which might contribute to develop therapeutic strategies for patients with ovulation failure-related disorders.

scholarly journals The Long and Short of It: The Role of Telomeres in Fetal Origins of Adult Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Stephanie E. Hallows ◽  
Timothy R. H. Regnault ◽  
Dean H. Betts
Keyword(s):  
Intrauterine Growth Restriction ◽  
The Body ◽  
Premature Aging ◽  
Fetal Origins ◽  
Maternal Malnutrition ◽  
Adult Disease ◽  
Increased Risk

Placental insufficiency, maternal malnutrition, and other causes of intrauterine growth restriction (IUGR) can significantly affect short-term growth and long-term health. Following IUGR, there is an increased risk for cardiovascular disease and Type 2 Diabetes. The etiology of these diseases is beginning to be elucidated, and premature aging or cellular senescence through increased oxidative stress and DNA damage to telomeric ends may be initiators of these disease processes. This paper will explore the areas where telomere and telomerase biology can have significant effects on various tissues in the body in IUGR outcomes.

scholarly journals Null mutations at the p66 and bradykinin 2 receptor loci induce divergent phenotypes in the diabetic kidney

2012 ◽  
Vol 303 (12) ◽  
pp. F1629-F1640 ◽  
Author(s):  
Himanshu Vashistha ◽  
Pravin C. Singhal ◽  
Ashwani Malhotra ◽  
Mohammad Husain ◽  
Peter Mathieson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Target Genes ◽  
Diabetic Glomerulosclerosis ◽  
Protein Levels ◽  
Urine Albumin ◽  
Increased Risk ◽  
Akita Mice ◽  
P53 Target Genes

Candidate genes have been identified that confer increased risk for diabetic glomerulosclerosis (DG). Mice heterozygous for the Akita (Ins2+/C96Y) diabetogenic mutation with a second mutation introduced at the bradykinin 2 receptor (B2R−/−) locus express a disease phenotype that approximates human DG. Src homology 2 domain transforming protein 1 (p66) controls mitochondrial metabolism and cellular responses to oxidative stress, aging, and apoptosis. We generated p66-null Akita mice to test whether inactivating mutations at the p66 locus will rescue kidneys of Akita mice from disease-causing mutations at the Ins2 and B2R loci. Here we show null mutations at the p66 and B2R loci interact with the Akita (Ins2+/C96Y) mutation, independently and in combination, inducing divergent phenotypes in the kidney. The B2R−/− mutation induces detrimental phenotypes, as judged by increased systemic and renal levels of oxidative stress, histology, and urine albumin excretion, whereas the p66-null mutation confers a powerful protection phenotype. To elucidate the mechanism(s) of the protection phenotype, we turned to our in vitro system. Experiments with cultured podocytes revealed previously unrecognized cross talk between p66 and the redox-sensitive transcription factor p53 that controls hyperglycemia-induced ROS metabolism, transcription of p53 target genes (angiotensinogen, angiotensin II type-1 receptor, and bax), angiotensin II generation, and apoptosis. RNA-interference targeting p66 inhibits all of the above. Finally, protein levels of p53 target genes were upregulated in kidneys of Akita mice but unchanged in p66-null Akita mice. Taken together, p66 is a potential molecular target for therapeutic intervention in DG.

scholarly journals A Review of the Potential for Cardiometabolic Dysfunction in Youth with Spina Bifida and the Role for Physical Activity and Structured Exercise

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Kevin R. Short ◽  
Dominic Frimberger
Keyword(s):  
Physical Activity ◽  
Spina Bifida ◽  
Cardiometabolic Risk ◽  
Metabolic Risk ◽  
Metabolic Dysfunction ◽  
Exercise Interventions ◽  
Adult Disease ◽  
Increased Risk

Children and adolescents who have decreased mobility due to spina bifida may be at increased risk for the components of metabolic syndrome, including abdominal obesity, insulin resistance, and dyslipidemia due to low physical activity. Like their nondisabled peers, adolescents with spina bifida that develop metabolic risk factors early in life have set the stage for adult disease. Exercise interventions can improve metabolic dysfunction in nondisabled youth, but the types of exercise programs that are most effective and the mechanisms involved are not known. This is especially true in adolescents with spina bifida, who have impaired mobility and physical function and with whom there have been few well-controlled studies. This paper highlights the current lack of knowledge about the role of physical activity and the need to develop exercise strategies targeting the reduction of cardiometabolic risk and improving quality of life in youth with spina bifida.

scholarly journals The role of heme oxygenase in metastatic melanoma tumorigenicity

2015 ◽  
Author(s):  
◽  
Kimberly J. Jasmer
Keyword(s):  
Oxidative Stress ◽  
Metastatic Melanoma ◽  
Heme Oxygenase ◽  
Focal Adhesion ◽  
Target Genes ◽  
Cancer Development ◽  
Heme Oxygenase Activity ◽  
Oxygenase Activity ◽  
Receptor Interactions

Reactive oxygen species (ROS) are highly reactive, tumorigenic molecules. In response to ROS accumulation, or oxidative stress, the transcription factor Nrf2 promotes expression by binding antioxidant response elements (AREs) found in the promoter of target genes. Traditionally, Nrf2 has been considered inhibitory of cancer by promoting the expression of phase II detoxifying enzymes, drug transporters, anti-apoptotic proteins, and proteasomes, which facilitate the removal of ROS and promote cell survival. Recently, however, overexpression of Nrf2-target genes has been implicated in promoting several cancer hallmarks and facilitating cancer development. Significant focus has been given to the role of Keap1/Nrf2 as a sensor for oxidative stress. Much less attention has been paid to the role of Bach1, a transcriptional repressor that competes with Nrf2 for ARE binding. The best-characterized Bach1 target is Heme Oxygenase-1 (HMOX1). While heme oxygenase inhibits cancer by preventing ROS-induced damage, mounting evidence suggests that HMOX1 overexpression at later stages in cancer development may promote cancer progression. Heme oxygenase catalyzes the degradation of heme and has two isozymes. HMOX1 is inducible by heme and oxidative stress while HMOX2 is constitutively expressed. Stage IV metastatic melanoma has a median survival of only 6 to 10 months. Unfortunately, current therapeutic approaches provide limited benefit in overall survival, highlighting the need for the identification of novel therapeutic targets. Activating mutations in B-Raf are found in approximately 70% of malignant melanomas. Using an anchorage-independent melanosphere assay, which is indicative of the tumorigenicity of melanoma cells, we found that activation of B-Raf, but not N-Ras, is a driver of melanosphere formation. We provide evidence that derepression of Bach1 by treatment with cobalt protoporphyrin IX (CoPP) is sufficient for melanosphere formation, and that melanosphere formation induced by either CoPP treatment or B-Raf activation is dependent on heme oxygenase activity. Global transcriptome analysis revealed enrichment for genes involved in focal adhesion and extracellular matrix (ECM)-receptor interactions following either B-Raf activation or treatment with CoPP. We propose a mechanism by which heme oxygenase promotes melanosphere formation, and by extension, enhanced tumorigenicity, by modulating expression of genes involved in focal adhesion and ECM-receptor interactions. Heme oxygenase activity may provide a novel therapeutic target for the treatment of metastatic melanoma.

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