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      Evaluation of the relationship among gene expressions and enzyme activities with antioxidant role and presenilin 1 expression in Alzheimer's disease

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          Abstract

          It is known that oxidative stress originating from reactive oxygen species plays a role in the pathogenesis of Alzheimer's disease. In this study, the role of antioxidant status associated with oxidative stress in Alzheimer's disease was investigated. Peripheral blood samples were obtained from 28 healthy individuals (as control) and 28 Alzheimer's patients who met the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria. Catalase, glutathione S‐transferase and paraoxonase 1 enzyme activities in blood plasma and glutathione S‐transferase enzyme activities in erythrocytes were determined by spectrophotometer. Catalase, glutathione S‐transferase and presenilin 1 gene expressions in leukocytes were determined using qRT‐PCR. Data were analysed with SPSS one‐way anova, a LSD post hoc test at p < 0.05. The activity of each enzyme was significantly reduced in Alzheimer's patients compared to control. The catalase gene expression level did not change compared to the control. Glutathione S‐transferase and presenilin 1 gene expression levels were increased compared to the control.

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          A new mathematical model for relative quantification in real-time RT-PCR.

          M. Pfaffl (2001)
          Use of the real-time polymerase chain reaction (PCR) to amplify cDNA products reverse transcribed from mRNA is on the way to becoming a routine tool in molecular biology to study low abundance gene expression. Real-time PCR is easy to perform, provides the necessary accuracy and produces reliable as well as rapid quantification results. But accurate quantification of nucleic acids requires a reproducible methodology and an adequate mathematical model for data analysis. This study enters into the particular topics of the relative quantification in real-time RT-PCR of a target gene transcript in comparison to a reference gene transcript. Therefore, a new mathematical model is presented. The relative expression ratio is calculated only from the real-time PCR efficiencies and the crossing point deviation of an unknown sample versus a control. This model needs no calibration curve. Control levels were included in the model to standardise each reaction run with respect to RNA integrity, sample loading and inter-PCR variations. High accuracy and reproducibility (<2.5% variation) were reached in LightCycler PCR using the established mathematical model.
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            Glutathione transferases.

            This review describes the three mammalian glutathione transferase (GST) families, namely cytosolic, mitochondrial, and microsomal GST, the latter now designated MAPEG. Besides detoxifying electrophilic xenobiotics, such as chemical carcinogens, environmental pollutants, and antitumor agents, these transferases inactivate endogenous alpha,beta-unsaturated aldehydes, quinones, epoxides, and hydroperoxides formed as secondary metabolites during oxidative stress. These enzymes are also intimately involved in the biosynthesis of leukotrienes, prostaglandins, testosterone, and progesterone, as well as the degradation of tyrosine. Among their substrates, GSTs conjugate the signaling molecules 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) and 4-hydroxynonenal with glutathione, and consequently they antagonize expression of genes trans-activated by the peroxisome proliferator-activated receptor gamma (PPARgamma) and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). Through metabolism of 15d-PGJ2, GST may enhance gene expression driven by nuclear factor-kappaB (NF-kappaB). Cytosolic human GST exhibit genetic polymorphisms and this variation can increase susceptibility to carcinogenesis and inflammatory disease. Polymorphisms in human MAPEG are associated with alterations in lung function and increased risk of myocardial infarction and stroke. Targeted disruption of murine genes has demonstrated that cytosolic GST isoenzymes are broadly cytoprotective, whereas MAPEG proteins have proinflammatory activities. Furthermore, knockout of mouse GSTA4 and GSTZ1 leads to overexpression of transferases in the Alpha, Mu, and Pi classes, an observation suggesting they are part of an adaptive mechanism that responds to endogenous chemical cues such as 4-hydroxynonenal and tyrosine degradation products. Consistent with this hypothesis, the promoters of cytosolic GST and MAPEG genes contain antioxidant response elements through which they are transcriptionally activated during exposure to Michael reaction acceptors and oxidative stress.
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              Free Radicals in Biology and Medicine

              Free Radicals in Biology and Medicine has become a classic text in the field of free radical and antioxidant research. Now in its fifth edition, the book has been comprehensively rewritten and updated whilst maintaining the clarity of its predecessors. Two new chapters discuss 'in vivo' and 'dietary' antioxidants, the first emphasising the role of peroxiredoxins and integrated defence mechanisms which allow useful roles for ROS, and the second containing new information on the role of fruits, vegetables, and vitamins in health and disease. This new edition also contains expanded coverage of the mechanisms of oxidative damage to lipids, DNA, and proteins (and the repair of such damage), and the roles played by reactive species in signal transduction, cell survival, death, human reproduction, defence mechanisms of animals and plants against pathogens, and other important biological events. The methodologies available to measure reactive species and oxidative damage (and their potential pitfalls) have been fully updated, as have the topics of phagocyte ROS production, NADPH oxidase enzymes, and toxicology. There is a detailed and critical evaluation of the role of free radicals and other reactive species in human diseases, especially cancer, cardiovascular, chronic inflammatory and neurodegenerative diseases. New aspects of ageing are discussed in the context of the free radical theory of ageing. This book is recommended as a comprehensive introduction to the field for students, educators, clinicians, and researchers. It will also be an invaluable companion to all those interested in the role of free radicals in the life and biomedical sciences.
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                Author and article information

                Contributors
                atunc@bingol.edu.tr
                Journal
                J Cell Mol Med
                J Cell Mol Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                29 September 2023
                November 2023
                : 27
                : 21 ( doiID: 10.1111/jcmm.v27.21 )
                : 3388-3394
                Affiliations
                [ 1 ] Department of Bioengineering, Faculty of Engineering Bilecik Şeyh Edebali University Bilecik Turkey
                [ 2 ] Department of Occupational Health and Safety, Faculty of Health Sciences Bingöl University Bingöl Turkey
                [ 3 ] Department of Medical Biochemistry, Faculty of Medicine Kafkas University Kars Turkey
                [ 4 ] Department of Anesthesia Regional Training and Research Hospital Erzurum Turkey
                [ 5 ] Department of Neurology Çekirge Public Hospital Bursa Turkey
                [ 6 ] Department of Neurology, Faculty of Medicine Atatürk University Erzurum Turkey
                [ 7 ] Department of Biochemistry, Faculty of Pharmacy Anadolu University Eskişehir Turkey
                Author notes
                [*] [* ] Correspondence

                Abdullah Tunç, Department of Occupational Health and Safety, Faculty of Health Sciences, Bingöl University, 12000 Bingöl, Turkey.

                Email: atunc@ 123456bingol.edu.tr

                Author information
                https://orcid.org/0000-0002-4677-8104
                https://orcid.org/0000-0002-2378-5897
                https://orcid.org/0000-0003-2080-0091
                https://orcid.org/0000-0002-7492-1975
                https://orcid.org/0000-0003-0828-520X
                https://orcid.org/0000-0003-3667-6902
                Article
                JCMM17953 JCMM-06-2023-042.R1
                10.1111/jcmm.17953
                10623531
                37772794
                81423c03-53b7-474d-acc8-dc9072ece86e
                © 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 August 2023
                : 05 June 2023
                : 01 September 2023
                Page count
                Figures: 2, Tables: 1, Pages: 7, Words: 4733
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                November 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.4 mode:remove_FC converted:03.11.2023

                Molecular medicine
                alzheimer's disease,antioxidant status,enzyme activity,gene expression,paraoxonase 1,presenilin 1

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