scholarly journals Power of Proteomics in Linking Oxidative Stress and Female Infertility

2014 ◽  
Vol 2014 ◽  
pp. 1-26 ◽  
Author(s):  
Sajal Gupta ◽  
Jana Ghulmiyyah ◽  
Rakesh Sharma ◽  
Jacques Halabi ◽  
Ashok Agarwal
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Unexplained Infertility ◽  
Female Infertility ◽  
Related Disease ◽  
Large Numbers ◽  
The One ◽  
Related Proteins ◽  
Potential Biomarkers

Endometriosis, PCOS, and unexplained infertility are currently the most common diseases rendering large numbers of women infertile worldwide. Oxidative stress, due to its deleterious effects on proteins and nucleic acids, is postulated to be the one of the important mechanistic pathways in differential expression of proteins and in these diseases. The emerging field of proteomics has allowed identification of proteins involved in cell cycle, as antioxidants, extracellular matrix (ECM), cytoskeleton, and their linkage to oxidative stress in female infertility related diseases. The aim of this paper is to assess the association of oxidative stress and protein expression in the reproductive microenvironments such as endometrial fluid, peritoneal fluid, and follicular fluid, as well as reproductive tissues and serum. The review also highlights the literature that proposes the use of the fertility related proteins as potential biomarkers for noninvasive and early diagnosis of the aforementioned diseases rather than utilizing the more invasive methods used currently. The review will highlight the power of proteomic profiles identified in infertility related disease conditions and their linkage with underlying oxidative stress. The power of proteomics will be reviewed with regard to eliciting molecular mechanisms for early detection and management of these infertility related conditions.

scholarly journals Molecular Mechanisms Underlying the Link between Diet and DNA Methylation

2018 ◽  
Vol 19 (12) ◽  
pp. 4055 ◽  
Author(s):  
Fatma Zehra Kadayifci ◽  
Shasha Zheng ◽  
Yuan-Xiang Pan
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Dna Demethylation ◽  
Direct Role ◽  
Large Numbers ◽  
Modifiable Factors ◽  
Activity Of Enzymes ◽  
Biochemical Mechanisms ◽  
The One

DNA methylation is a vital modification process in the control of genetic information, which contributes to the epigenetics by regulating gene expression without changing the DNA sequence. Abnormal DNA methylation—both hypomethylation and hypermethylation—has been associated with improper gene expression, leading to several disorders. Two types of risk factors can alter the epigenetic regulation of methylation pathways: genetic factors and modifiable factors. Nutrition is one of the strongest modifiable factors, which plays a direct role in DNA methylation pathways. Large numbers of studies have investigated the effects of nutrition on DNA methylation pathways, but relatively few have focused on the biochemical mechanisms. Understanding the biological mechanisms is essential for clarifying how nutrients function in epigenetics. It is believed that nutrition affects the epigenetic regulations of DNA methylation in several possible epigenetic pathways: mainly, by altering the substrates and cofactors that are necessary for proper DNA methylation; additionally, by changing the activity of enzymes regulating the one-carbon cycle; and, lastly, through there being an epigenetic role in several possible mechanisms related to DNA demethylation activity. The aim of this article is to review the potential underlying biochemical mechanisms that are related to diet modifications in DNA methylation and demethylation.

scholarly journals Oxidative Stress in Myopia

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Bosch-Morell Francisco ◽  
Mérida Salvador ◽  
Navea Amparo
Keyword(s):  
Oxidative Stress ◽  
Retinal Detachment ◽  
High Myopia ◽  
Molecular Mechanisms ◽  
Medical Problem ◽  
Regulatory Pathways ◽  
Eye Growth ◽  
Genetic And Environmental Factors ◽  
The One ◽  
Macular Hemorrhage

Myopia affected approximately 1.6 billion people worldwide in 2000, and it is expected to increase to 2.5 billion by 2020. Although optical problems can be corrected by optics or surgical procedures, normal myopia and high myopia are still an unsolved medical problem. They frequently predispose people who have them to suffer from other eye pathologies: retinal detachment, glaucoma, macular hemorrhage, cataracts, and so on being one of the main causes of visual deterioration and blindness. Genetic and environmental factors have been associated with myopia. Nevertheless, lack of knowledge in the underlying physiopathological molecular mechanisms has not permitted an adequate diagnosis, prevention, or treatment to be found. Nowadays several pieces of evidence indicate that oxidative stress may help explain the altered regulatory pathways in myopia and the appearance of associated eye diseases. On the one hand, oxidative damage associated with hypoxia myopic can alter the neuromodulation that nitric oxide and dopamine have in eye growth. On the other hand, radical superoxide or peroxynitrite production damage retina, vitreous, lens, and so on contributing to the appearance of retinopathies, retinal detachment, cataracts and so on. The objective of this review is to suggest that oxidative stress is one of the key pieces that can help solve this complex eye problem.

scholarly journals MicroRNA-204-5p reduction in rat hippocampus contributes to stress-induced pathology via targeting RGS12 signaling pathway

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian Lan ◽  
Ye Li ◽  
Cuiqin Fan ◽  
Liyan Wang ◽  
Wenjing Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Immunofluorescence Assay ◽  
Electrophysiological Recording ◽  
Protein Signaling ◽  
Oxidative Markers ◽  
Electron Microscopy Analysis ◽  
Stress Damage ◽  
Related Proteins

Abstract Background Neuroinflammation occupies a pivotal position in the pathogenesis of most nervous system diseases, including depression. However, the underlying molecular mechanisms of neuroinflammation associated with neuronal injury in depression remain largely uncharacterized. Therefore, identifying potential molecular mechanisms and therapeutic targets would serve to better understand the progression of this condition. Methods Chronic unpredictable stress (CUS) was used to induce depression-like behaviors in rats. RNA-sequencing was used to detect the differentially expressed microRNAs. Stereotactic injection of AAV virus to overexpress or knockdown the miR-204-5p. The oxidative markers and inflammatory related proteins were verified by immunoblotting or immunofluorescence assay. The oxidative stress enzyme and products were verified using enzyme-linked assay kit. Electron microscopy analysis was used to observe the synapse and ultrastructural pathology. Finally, electrophysiological recording was used to analyze the synaptic transmission. Results Here, we found that the expression of miR-204-5p within the hippocampal dentate gyrus (DG) region of rats was significantly down-regulated after chronic unpredicted stress (CUS), accompanied with the oxidative stress-induced neuronal damage within DG region of these rats. In contrast, overexpression of miR-204-5p within the DG region of CUS rats alleviated oxidative stress and neuroinflammation by directly targeting the regulator of G protein signaling 12 (RGS12), effects which were accompanied with amelioration of depressive-like behaviors in these CUS rats. In addition, down-regulation of miR-204-5p induced neuronal deterioration in DG regions and depressive-like behaviors in rats. Conclusion Taken together, these results suggest that miR-204-5p plays a key role in regulating oxidative stress damage in CUS-induced pathological processes of depression. Such findings provide evidence of the involvement of miR-204-5p in mechanisms underlying oxidative stress associated with depressive phenotype. Graphical Abstract

scholarly journals LncRNA-T199678 Mitigates α-Synuclein-Induced Dopaminergic Neuron Injury via miR-101-3p

2020 ◽  
Vol 12 ◽  
Author(s):  
Lu-Lu Bu ◽  
Ying-Yu Xie ◽  
Dan-Yu Lin ◽  
Ying Chen ◽  
Xiu-Na Jing ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Dopaminergic Neuron ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Molecular Target ◽  
Neuron Death ◽  
Abnormal Accumulation ◽  
Neuron Injury

Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by dopaminergic neuron death and the abnormal accumulation and aggregation of α-synuclein (α-Syn) in the substantia nigra (SN). Although the abnormal accumulation of α-Syn can solely promote and accelerate the progress of PD, the underlying molecular mechanisms remain unknown. Mounting evidence confirms that the abnormal expression of long non-coding RNA (lncRNA) plays an important role in PD. Our previous study found that exogenous α-Syn induced the downregulation of lncRNA-T199678 in SH-SY5Y cells via a gene microarray analysis. This finding suggested that lncRNA-T199678 might have a potential pathological role in the pathogenesis of PD. This study aimed to explore the influence of lncRNA-T199678 on α-Syn-induced dopaminergic neuron injury. Overexpression of lncRNA-T199678 ameliorated the neuron injury induced by α-Syn via regulating oxidative stress, cell cycle, and apoptosis. Studies indicate lncRNAs could regulate posttranscriptional gene expression via regulating the downstream microRNA (miRNA). To discover the downstream molecular target of lncRNA-T199678, the following experiment found out that miR-101-3p was a potential target for lncRNA-T199678. Further study showed that the upregulation of lncRNA-T199678 reduced α-Syn-induced neuronal damage through miR-101-3p in SH-SY5Y cells and lncRNA-T199678 was responsible for the α-Syn-induced intracellular oxidative stress, dysfunction of the cell cycle, and apoptosis. All in all, lncRNA-T199678 mitigated the α-Syn-induced dopaminergic neuron injury via targeting miR-101-3p, which contributed to promote PD. Our results highlighted the role of lncRNA-T199678 in mitigating dopaminergic neuron injury in PD and revealed a new molecular target for PD.

scholarly journals Hongjingtian Injection Attenuates Myocardial Oxidative Damage via Promoting Autophagy and Inhibiting Apoptosis

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Shujing Zhang ◽  
Ling Zhang ◽  
Han Zhang ◽  
Guanwei Fan ◽  
Jiuwen Qiu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Disease ◽  
Oxidative Damage ◽  
Molecular Mechanisms ◽  
Mitochondrial Oxygen Consumption ◽  
Associated Proteins ◽  
Botanical Drug ◽  
Cardiomyocyte Autophagy ◽  
Induced Apoptosis ◽  
Related Proteins

Natural products with antioxidative activities are widely applied to prevent and treat various oxidative stress related diseases, including ischemic heart disease. However, the cellular and molecular mechanisms of those therapies are still needed to be illustrated. In this study, we characterized the cardioprotective effects of Hongjingtian Injection (HJT), an extensively used botanical drug for treating coronary heart disease. The H/R-induced profound elevation of oxidative stress was suppressed by HJT. HJT also attenuates oxidative injury by promoting cell viability, intracellular ATP contents, and mitochondrial oxygen consumption. Validation experiments indicated that HJT inhibited H/R-induced apoptosis and regulated the expression of apoptosis-associated proteins Bcl-2 and cleaved caspase3. Interestingly, HJT significantly regulated the expression of autophagy-related proteins LC3, Beclin, and mTOR as well as ERK and AKT. We provide evidence that the mechanism involves activation of AKT/Beclin-1, AKT, and ERK/mTOR pathway in cardiomyocyte autophagy. Histological and physiological evaluation revealed that HJT significantly decreased the infarct area of the heart, improved cardiac function, and increased the expression of LC3B in a rat model of coronary occlusion. From the obtained data, we proposed that HJT diminished myocardial oxidative damage through regulating the balance of autophagy and apoptosis and reducing oxidative stress.

scholarly journals p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shun Kageyama ◽  
Sigurdur Runar Gudmundsson ◽  
Yu-Shin Sou ◽  
Yoshinobu Ichimura ◽  
Naoki Tamura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Oxidative Stress Response ◽  
Liquid Droplets ◽  
Autophagosome Formation ◽  
Selective Autophagy ◽  
Selective Degradation ◽  
Physiological Relevance ◽  
Related Proteins

AbstractAutophagy contributes to the selective degradation of liquid droplets, including the P-Granule, Ape1-complex and p62/SQSTM1-body, although the molecular mechanisms and physiological relevance of selective degradation remain unclear. In this report, we describe the properties of endogenous p62-bodies, the effect of autophagosome biogenesis on these bodies, and the in vivo significance of their turnover. p62-bodies are low-liquidity gels containing ubiquitin and core autophagy-related proteins. Multiple autophagosomes form on the p62-gels, and the interaction of autophagosome-localizing Atg8-proteins with p62 directs autophagosome formation toward the p62-gel. Keap1 also reversibly translocates to the p62-gels in a p62-binding dependent fashion to activate the transcription factor Nrf2. Mice deficient for Atg8-interaction-dependent selective autophagy show that impaired turnover of p62-gels leads to Nrf2 hyperactivation in vivo. These results indicate that p62-gels are not simple substrates for autophagy but serve as platforms for both autophagosome formation and anti-oxidative stress.

scholarly journals The Mitochondrial Metabolic Checkpoint and Reversing Stem Cell Aging

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. SCI-34-SCI-34
Author(s):  
Danica Chen
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Stem Cell ◽  
Molecular Mechanisms ◽  
Conflicts Of Interest ◽  
Mitochondrial Protein ◽  
Cell Aging ◽  
Quiescent State ◽  
Mitochondrial Oxidative Stress ◽  
Hematopoietic Stem

Abstract Cell cycle checkpoints are surveillance mechanisms in eukaryotic cells that monitor the condition of the cell, repair cellular damages, and allow the cell to progress through the various phases of the cell cycle when conditions become favorable. Recent advances in hematopoietic stem cell (HSC) biology highlight a mitochondrial metabolic checkpoint that is essential for HSCs to return to the quiescent state. As quiescent HSCs enter the cell cycle, mitochondrial biogenesis is induced, which is associated with increased mitochondrial protein folding stress and mitochondrial oxidative stress. Mitochondrial unfolded protein response and mitochondrial oxidative stress response are activated to alleviate stresses and allow HSCs to exit the cell cycle and return to quiescence. Other mitochondrial maintenance mechanisms include mitophagy and asymmetric segregation of aged mitochondria. Because loss of HSC quiescence results in the depletion of the HSC pool and compromised tissue regeneration, deciphering the molecular mechanisms that regulate the mitochondrial metabolic checkpoint in HSCs will increase our understanding of hematopoiesis and how it becomes dysregulated under pathological conditions and during aging. More broadly, this knowledge is instrumental for understanding the maintenance of cells that convert between quiescence and proliferation to support their physiological functions. Disclosures No relevant conflicts of interest to declare.

scholarly journals Assessment of molecular mechanisms and potential biomarkers in bladder urothelial carcinoma

Acta Medica ◽  
2019 ◽  
Vol 50 (2) ◽  
pp. 8-15
Author(s):  
Ceren Sucularlı
Keyword(s):  
Cell Cycle ◽  
Urothelial Carcinoma ◽  
Molecular Mechanisms ◽  
Patient Survival ◽  
Smooth Muscle Contraction ◽  
Receptor Interaction ◽  
Ppi Networks ◽  
Normal Bladder ◽  
Bladder Urothelial Carcinoma ◽  
Potential Biomarkers

Objective: Bladder cancer ranks 10th among the most common cancers worldwide, effecting mostly man than women. The aim of this study is to perform a detailed gene expression analysis of bladder urothelial carcinoma to reveal altered molecular mechanisms and to find potential biomarkers for this cancer. Materials and Methods: Bladder urothelial carcinoma RNA-seq data from TCGA and normal bladder samples from GTEx were analyzed by using GEPIA. Differentially expressed genes were annotated to GO-BP and KEGG pathway terms with DAVID and PPI networks were constructed by STRING. The association of upregulated cell cycle pathway proteins and patient survival was further investigated. Results: Upregulated genes mainly annotated to cell cycle, p53 signaling and oocyte meiosis and maturation pathways and cell cycle related GO-BP terms. Downregulated genes mostly annotated to adhesion, ECM-receptor interaction, vascular smooth muscle contraction and cardiomyopathy related KEGG pathways and muscle related GO-BP terms. The protein products of six cell cycle genes, which were upregulated in bladder urothelial carcinoma, showed significant association with patient survival. Conclusion: The results of this study showed altered molecular mechanisms and increased our understanding in bladder urothelial carcinoma, proposed potential prognostic biomarkers.  

scholarly journals Changes in Mitochondrial Genome Associated with Predisposition to Atherosclerosis and Related Disease

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 377 ◽  
Author(s):  
Aleksandrina Volobueva ◽  
Andrey Grechko ◽  
Shaw-Fang Yet ◽  
Igor Sobenin ◽  
Alexander Orekhov
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dna ◽  
Molecular Markers ◽  
Cardiovascular Diseases ◽  
Mitochondrial Genome ◽  
Therapeutic Intervention ◽  
Molecular Mechanisms ◽  
Disease Pathogenesis ◽  
Mtdna Mutations ◽  
Related Disease

Atherosclerosis-related cardiovascular diseases remain the leading cause of morbidity and mortality, and the search for novel diagnostic and therapeutic methods is ongoing. Mitochondrial DNA (mtDNA) mutations associated with atherosclerosis represent one of the less explored aspects of the disease pathogenesis that may bring some interesting opportunities for establishing novel molecular markers and, possibly, new points of therapeutic intervention. Recent studies have identified a number of mtDNA mutations, for which the heteroplasmy level was positively or negatively associated with atherosclerosis, including the disease at its early, subclinical stages. In this review, we summarize the results of these studies, providing a list of human mtDNA mutations potentially involved in atherosclerosis. The molecular mechanisms underlying such involvement remain to be elucidated, although it is likely that some of them may be responsible for the increased oxidative stress, which plays an important role in atherosclerosis.

P1890Pioglitazone inhibits diabetes-induced atrial mitochondrial oxidative stress and improves mitochondrial biogenesis, dynamics and function through the PGC-1 signaling pathway

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Liu ◽  
Z Zhang ◽  
X Zhang ◽  
L Meng ◽  
M Gong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Protein Expression ◽  
Molecular Mechanisms ◽  
Mitochondrial Morphology ◽  
Atrial Remodeling ◽  
Ppar Γ ◽  
And Function ◽  
Related Proteins ◽  
Tgf Β1

Abstract Background Oxidative stress contributes to adverse atrial remodeling in diabetes mellitus. This can be prevented by the PPAR-γ agonist pioglitazone through its anti-oxidant and anti-inflammatory effects. Purpose In this study, the molecular mechanisms underlying these effects were investigated. Methods Rabbits were randomly divided into control (C), diabetic (DM), and pioglitazone-treated DM (Pio) groups. Echocardiographic, hemodynamic, electrophysiological, intracellular Ca2+ properties were measured. Serum PPAR-γ levels, serum and tissue oxidative stress and inflammatory markers, mitochondrial morphology, reactive oxygen species (ROS) production rate, respiratory function, and mitochondrial membrane potential (MMP) levels were measured. Protein expression of pro-fibrotic marker transforming growth factor β1 (TGF-β1), and the mitochondrial proteins (PGC-1α, fission and fusion-related proteins) were measured. Results Compared with controls, the DM group demonstrated larger left atrial diameter and fibrosis area associated with a higher incidence of inducible AF. Lower serum PPAR-γ level was associated with lower PGC-1α, higher NF-κB and higher TGF-β1 expression. Mn-SOD protein was not different but lower mitochondrial fission- and fusion-related proteins were detected. Mitochondrial swelling, higher mitochondrial ROS, lower respiratory control rate, lower MMP and higher intracellular Ca2+ transients were observed. In the Pio group, reversal of structural remodeling and lower inducible AF incidence were associated with higher PPAR-γ and PGC-1α. NF-κB and TGF-β1 were lower and biogenesis, fission and fusion-related protein were higher. Mitochondrial structure and function, and intracellular Ca2+ transients were improved. In HL-1 cell line, transfected with PGC-1α siRNA blunted the effect of pioglitazone on Mn-SOD protein expression and MMP collapse in H2O2-treated cells. Conclusion Diabetes mellitus induces adverse atrial structural and electrophysiological remodeling, abnormal Ca2+ handling and mitochondrial damage and dysfunction. Pioglitazone prevented these abnormalities through the PPAR-γ/PGC-1α pathway. Acknowledgement/Funding National Natural Science Foundation of China (No 81570298, 81270245, 30900618 to T.L.)

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