scholarly journals Hydroxyl Radical Damaged Thymidine-5’-Monophophate Presents Unique Epitopes for Cancer Antibodies

2009 ◽  
Vol 2 (1) ◽  
pp. 10-17 ◽  
Author(s):  
Rizwan Ahmad ◽  
Zafar Rasheed ◽  
Rashid Ali
Keyword(s):  
Hydroxyl Radical ◽  
Cancer Patients ◽  
Structural Changes ◽  
Competitive Inhibition ◽  
Specific Binding ◽  
Protein A ◽  
Oxygen Species ◽  
Direct Binding ◽  
High Degree

Reactive oxygen species (ROS) plays an important role in carcinogenesis and hydroxyl radical (OH) contributes to the structural changes in DNA that characterize the cancer like phenotype. The role of hydroxyl radical (OH) damaged thymidine 5'-monophosphate (TMP) in cancer patients has been investigated in the present study. TMP was conjugated to bovine serum albumin (BSA), and then TMP-BSA conjugate was modified by hydroxyl radicals. Cancer patients (n = 99) were screened by direct binding ELISA for the detection of antibodies against native and ROS-modified conjugates and the results were compared with healthy age-matched controls (n = 29). High degree of specific binding by cancer serum antibodies towards ROS modified TMP-BSA conjugate, in comparison to unmodified conjugate (p<0.05) was observed. Healthy individuals showed negligible binding with either antigen. Competitive inhibition ELISA reiterates the direct binding results. Protein-A affinity purified IgG from cancer patients further substantiated the enhanced recognition towards modified conjugate as compared to unmodified conjugate. The present study clearly shows the perturbation in TMP-BSA conjugate by hydroxyl radical presenting unique neo-epitopes on TMP that might from one of the factors in antigen driven induction of antibodies in cancer patients.

scholarly journals Antibodies against 4-Hydroxy-2-nonenal Modified Epitopes Recognized Chromatin and Its Oxidized Forms: Role of Chromatin, Oxidized Forms of Chromatin and 4-Hydroxy-2-nonenal Modified Epitopes in the Etiopathogenesis of SLE

2012 ◽  
Vol 33 (1) ◽  
pp. 19-34 ◽  
Author(s):  
Hani A. Al-Shobaili ◽  
Ahmad A. Al Robaee ◽  
Abdullateef A. Alzolibani ◽  
Zafar Rasheed
Keyword(s):  
Lupus Erythematosus ◽  
Specific Binding ◽  
Polyclonal Antibodies ◽  
Protein A ◽  
Oxygen Species ◽  
Systemic Lupus ◽  
Specific Antibodies ◽  
High Degree ◽  
Insight Into

Objectives:This study was undertaken to investigate the role of lipid oxidative-by-product 4-hydroxy-2-nonenal (HNE)-modified human serum albumin (HSA), chromatin, reactive oxygen species (ROS)-modified chromatin and nitric oxide (NO)-modified chromatin in systemic lupus erythematosus (SLE).Methods:HSA was modified by HNE. Immunogenicity of modified HSA was probed by inducing polyclonal antibodies in rabbits. Chromatin was isolated from goat liver and modified by ROS or NO. Immunocross-reactions of Protein-A purified anti-HNE-HSA-IgG with chromatin, ROS-chromatin and NO-chromatin were determined. Autoantibodies from 74 SLE patients were screened. HSA was isolated from SLE patients (SLE-HSA) and immunocross-reactions of isolated SLE-HSA with HNE-specific antibodies were investigated.Results:HNE-HSA was found to be highly immunogenic in rabbits. The notable feature of anti-HNE-HSA-IgG showed cross-reactions with chromatin, ROS-chromatin and NO-chromatin (p< 0.01). High degree of specific binding to HNEHSA, chromatin, ROS-chromatin or NO-chromatin was observed with antibodies from 55% of SLE patients. SLE anti-native/oxidized chromatin antibodies showed specificity towards HNE-HSA. Furthermore, SLE-HSAshowed binding with HNE-specific antibodies.Conclusions:This is the first study to demonstrate that chromatin and its oxidized forms have been recognized by antibodies against HNE modified epitopes. Our results provide an important insight into the immunological basis of the reported HNE-modified epitopes in SLE.

scholarly journals Ferroptosis in plants: triggers, proposed mechanisms, and the role of iron in modulating cell death

2020 ◽  
Author(s):  
Ayelén Mariana Distéfano ◽  
Gabriel Alejandro López ◽  
Nicolás Setzes ◽  
Fernanda Marchetti ◽  
Maximiliano Cainzos ◽  
...  
Keyword(s):  
Cell Death ◽  
Metabolic Pathways ◽  
Oxygen Species ◽  
Cell Death Pathway ◽  
Plant Life ◽  
Regulated Cell Death ◽  
Dependent Cell ◽  
Plant Life Cycle ◽  
High Degree

Abstract Regulated cell death plays key roles during essential processes throughout the plant life cycle. It takes part in specific developmental programs and maintains homeostasis of the organism in response to unfavorable environments. Ferroptosis is a recently discovered iron-dependent cell death pathway characterized by the accumulation of lipid reactive oxygen species. In plants, ferroptosis shares all the main hallmarks described in other systems. Those specific features include biochemical and morphological signatures that seem to be conserved among species. However, plant cells have specific metabolic pathways and a high degree of metabolic compartmentalization. Together with their particular morphology, these features add more complexity to the plant ferroptosis pathway. In this review, we summarize the most recent advances in elucidating the roles of ferroptosis in plants, focusing on specific triggers, the main players, and underlying pathways.

scholarly journals Dual Role of ROS as Signal and Stress Agents: Iron Tips the Balance in favor of Toxic Effects

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Elena Gammella ◽  
Stefania Recalcati ◽  
Gaetano Cairo
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Oxidative Damage ◽  
Cell Signaling ◽  
Hydroxyl Radical ◽  
Iron Homeostasis ◽  
Storage Proteins ◽  
Oxygen Species ◽  
Physiologic Role

Iron is essential for life, while also being potentially harmful. Therefore, its level is strictly monitored and complex pathways have evolved to keep iron safely bound to transport or storage proteins, thereby maintaining homeostasis at the cellular and systemic levels. These sequestration mechanisms ensure that mildly reactive oxygen species like anion superoxide and hydrogen peroxide, which are continuously generated in cells living under aerobic conditions, keep their physiologic role in cell signaling while escaping iron-catalyzed transformation in the highly toxic hydroxyl radical. In this review, we describe the multifaceted systems regulating cellular and body iron homeostasis and discuss how altered iron balance may lead to oxidative damage in some pathophysiological settings.

scholarly journals Role of P63 (CKAP4) in binding of surfactant protein-A to type II pneumocytes

2008 ◽  
Vol 295 (4) ◽  
pp. L658-L669 ◽  
Author(s):  
Sandra R. Bates ◽  
Altaf S. Kazi ◽  
Jian-Qin Tao ◽  
Kevin J. Yu ◽  
Daniel S. Gonder ◽  
...  
Keyword(s):  
Specific Binding ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Type Ii Cells ◽  
Type Ii ◽  
Calcium Dependent ◽  
Type Ii Pneumocytes ◽  
Surfactant Secretion

We have recently described a putative receptor for lung surfactant protein-A (SP-A) on rat type II pneumocytes. The receptor, P63, is a 63-kDa type II transmembrane protein. Coincubation of type II cells with P63 antibody (Ab) reversed the inhibitory effect of SP-A on secretagogue-stimulated surfactant secretion from type II cells. To further characterize SP-A interactions with P63, we expressed recombinant P63 protein in Escherichia coli and generated antibodies to P63. Immunogold electron microscopy confirmed endoplasmic reticulum and plasma membrane localization of P63 in type II cells with prominent labeling of microvilli. Binding characteristics of iodinated SP-A to type II cells in the presence of P63 Ab were determined. Binding (4°C, 1 h) of 125I-SP-A to type II cells demonstrated both specific (calcium-dependent) and nonspecific (calcium-independent) components. Ab to P63 protein blocked the specific binding of 125I-SP-A to type II cells and did not change the nonspecific SP-A association. A549 cells, a pneumocyte model cell line, expressed substantial levels of P63 and demonstrated specific binding of 125I-SP-A that was inhibited by the P63 Ab. The secretagogue (cAMP)-stimulated increase in calcium-dependent binding of SP-A to type II cells was blocked by the presence of P63 Ab. Transfection of type II cells with small interfering RNA to P63 reduced P63 protein expression, attenuated P63-specific SP-A binding, and reversed the ability of SP-A to prevent surfactant secretion from the cells. Our results further substantiate the role of P63 as an SP-A receptor protein localized on the surface of lung type II cells.

scholarly journals Pituitary Homeobox 1 Activates the Rat FSHβ (rFSHβ) Gene through Both Direct and Indirect Interactions with the rFSHβ Gene Promoter

2002 ◽  
Vol 16 (8) ◽  
pp. 1840-1852 ◽  
Author(s):  
Marjorie M. Zakaria ◽  
Kyeong-Hoon Jeong ◽  
Charlemagne Lacza ◽  
Ursula B. Kaiser
Keyword(s):  
Gene Expression ◽  
Binding Sites ◽  
Hormonal Regulation ◽  
Molecular Mechanisms ◽  
Specific Binding ◽  
Gene Promoter ◽  
Functional Studies ◽  
Direct Binding ◽  
Residual Activation

Abstract Molecular mechanisms underlying gonadotrope-specific and hormonal regulation of FSHβ gene expression remain largely unknown. We have studied the role of pituitary homeobox 1 (Ptx1), a transcription factor important for regulation of many pituitary-specific genes, in the regulation of rat FSHβ (rFSHβ) gene transcription. We demonstrate that Ptx1 activates the rFSHβ gene promoter both basally and in synergy with GnRH. The effect of Ptx1 was localized to −140/−50, a region also important for basal activity of the promoter. Two putative Ptx1 binding sites (P1 and P2) homologous to consensus Ptx1 binding elements were identified in this region. We demonstrate specific binding of Ptx1 to the P2 but not to the P1 site. Furthermore, functional studies indicate that the P2 but not the P1 site mediates activation of the promoter by Ptx1. Residual activation of the promoter by Ptx1 was observed independent of the P2 site. However, no additional Ptx1 binding sites were identified in this region, indicating that the residual activation observed is likely independent of direct Ptx1 binding to the promoter. These results identify a functional Ptx1 binding site in the rFSHβ gene promoter and suggest the presence of an additional activating pathway that is independent of direct binding of Ptx1 to the promoter.

scholarly journals The role of ATP in the function of human ORC4 protein

2010 ◽  
Vol 75 (3) ◽  
pp. 317-322
Author(s):  
Aleksandra Divac ◽  
Branko Tomic ◽  
Jelena Kusic
Keyword(s):  
Conformational Changes ◽  
Origin Recognition Complex ◽  
Structural Changes ◽  
Atp Hydrolysis ◽  
Protein A ◽  
Structural Role ◽  
A Subunit ◽  
Dna Substrates ◽  
Origin Recognition

Human ORC4 protein, a subunit of the origin recognition complex, belongs to the AAA+ superfamily of ATPases. Proteins belonging to this family require ATP for their function and interactions with ATP lead to conformational changes in them or in their partners. Human ORC4 protein induces structural changes in DNA substrates, promoting renaturation and formation of non-canonical structures, as well as conversion of single-stranded into multi-stranded oligonucleotide structures. The aim of this study was to further investigate the role of ATP in the function of human ORC4 protein. For this purpose, a mutant in the conserved Walker B motif of ORC4, which is able to bind but not to hydrolyze ATP, was constructed and its activity in DNA restructuring reactions was investigated. The obtained results showed that ATP hydrolysis is not necessary for the function of human ORC4. It is proposed that ATP has a structural role as a cofactor in the function of human ORC4 as a DNA restructuring agent.

The Ubaid Period In The Urbanisation Process; The Birth Of Urbanism In The Near East (5500-3800 B.C.)

Belleten ◽  
2008 ◽  
Vol 72 (264) ◽  
pp. 395-412
Author(s):  
Alev Erarslan
Keyword(s):  
Crucial Role ◽  
Structural Changes ◽  
Social Economic ◽  
Near East ◽  
Technological Development ◽  
Complex Societies ◽  
The Social ◽  
Process Of Urbanization ◽  
High Degree

The Ubaid culture, which takes its name from Tell-al Ubaid, plays a crucial role in the process of urbanization in the Near East. Surviving for more than 1500 years (5500-3800 BC), it was characterised by important social, economic and political developments which influenced the development of urban polities both the Near East and the East and Southeastern Anatolia Regions. With this culture, certain radical structural changes peculiar to complex societies, urban societies, such as political and economic centralisation based on control over product, production and labor organisation with sealing practices, socio-economic differences, a high degree of economic specialisation and technological development, indicate that a complex economy, and organised trade had begun to take place in the social, political and economical organisations of the societies of the Near East. This paper is concerned with enlightening the role of the Ubaid Culture in the development of urban societies in the Near East. With this aim, this culture will be analyzed from the viewpoint of those characteristics peculiar to urban societies mentioned above.

scholarly journals Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2382
Author(s):  
Sepideh Mirzaei ◽  
Kiavash Hushmandi ◽  
Amirhossein Zabolian ◽  
Hossein Saleki ◽  
Seyed Mohammad Reza Torabi ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Effective Treatment ◽  
Cancer Patients ◽  
Reactive Oxygen ◽  
Molecular Pathways ◽  
Oxygen Species ◽  
Interfering Rna ◽  
The Relationship ◽  
Anti Tumor Activity

The failure of chemotherapy is a major challenge nowadays, and in order to ensure effective treatment of cancer patients, it is of great importance to reveal the molecular pathways and mechanisms involved in chemoresistance. Cisplatin (CP) is a platinum-containing drug with anti-tumor activity against different cancers in both pre-clinical and clinical studies. However, drug resistance has restricted its potential in the treatment of cancer patients. CP can promote levels of free radicals, particularly reactive oxygen species (ROS) to induce cell death. Due to the double-edged sword role of ROS in cancer as a pro-survival or pro-death mechanism, ROS can result in CP resistance. In the present review, association of ROS with CP sensitivity/resistance is discussed, and in particular, how molecular pathways, both upstream and downstream targets, can affect the response of cancer cells to CP chemotherapy. Furthermore, anti-tumor compounds, such as curcumin, emodin, chloroquine that regulate ROS and related molecular pathways in increasing CP sensitivity are described. Nanoparticles can provide co-delivery of CP with anti-tumor agents and by mediating photodynamic therapy, and induce ROS overgeneration to trigger CP sensitivity. Genetic tools, such as small interfering RNA (siRNA) can down-regulate molecular pathways such as HIF-1α and Nrf2 to promote ROS levels, leading to CP sensitivity. Considering the relationship between ROS and CP chemotherapy, and translating these findings to clinic can pave the way for effective treatment of cancer patients.

scholarly journals Role of atmospheric oxidation in recent methane growth

2017 ◽  
Vol 114 (21) ◽  
pp. 5373-5377 ◽  
Author(s):  
Matthew Rigby ◽  
Stephen A. Montzka ◽  
Ronald G. Prinn ◽  
James W. C. White ◽  
Dickon Young ◽  
...  
Keyword(s):  
Hydroxyl Radical ◽  
Industrial Revolution ◽  
Systematic Uncertainties ◽  
Atmospheric Observations ◽  
Primary Driver ◽  
Degree Of Confidence ◽  
Recent Trends ◽  
High Degree ◽  
Year 2000

The growth in global methane (CH4) concentration, which had been ongoing since the industrial revolution, stalled around the year 2000 before resuming globally in 2007. We evaluate the role of the hydroxyl radical (OH), the major CH4 sink, in the recent CH4 growth. We also examine the influence of systematic uncertainties in OH concentrations on CH4 emissions inferred from atmospheric observations. We use observations of 1,1,1-trichloroethane (CH3CCl3), which is lost primarily through reaction with OH, to estimate OH levels as well as CH3CC3 emissions, which have uncertainty that previously limited the accuracy of OH estimates. We find a 64–70% probability that a decline in OH has contributed to the post-2007 methane rise. Our median solution suggests that CH4 emissions increased relatively steadily during the late 1990s and early 2000s, after which growth was more modest. This solution obviates the need for a sudden statistically significant change in total CH4 emissions around the year 2007 to explain the atmospheric observations and can explain some of the decline in the atmospheric 13CH4/12CH4 ratio and the recent growth in C2H6. Our approach indicates that significant OH-related uncertainties in the CH4 budget remain, and we find that it is not possible to implicate, with a high degree of confidence, rapid global CH4 emissions changes as the primary driver of recent trends when our inferred OH trends and these uncertainties are considered.

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