Abstract
Protein damage mediated by oxidation has been associated with aging and age-related diseases, in particular neurodegenerative diseases. The protein that is known to be one of the major targets of oxidative stress is glyceraldehyde- 3-phosphate dehydrogenase. GAPDH is believed to play a key role in certain neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. Several recent studies have suggested that a wide range of variety of polyphenols including resveratrol may have neuroprotective effects. Here, we present data that clearly indicate the prooxidative properties of resveratrol and tiron in the inactivation of GAPDH induced by the superoxide anion generated via xanthine oxidase mediated oxidation of xanthine. Generated in the studied system tiron and resveratrol radicals are much more efficient in the inactivation of GAPDH than the superoxide anion alone. The analysis of CD spectra of protein exposed to the tiron and resveratrol radicals revealed little effect on the secondary structure of GAPDH. In both cases reduction of α-helical structure was followed by the increase in β-sheet conformation. Thus, the most probable mechanism of inactivation of GAPDH in the studied system is oxidation of cysteine residues in the catalytic center of the enzyme. Finally, molecular modeling of the resveratrol - GAPDH and tiron - GAPDH complexes showed potential binding sites for those antioxidants with binding affinity -45 kcal/mol and -48 kcal/mol respectively.
Keywords: GAPDH, antioxidant, resveratrol, tiron, protein damage, superoxide anion radical.
Current Medicinal Chemistry
Title:Effect of Resveratrol and Tiron on the Inactivation of Glyceraldehyde-3- phosphate Dehydrogenase Induced by Superoxide Anion Radical
Volume: 21 Issue: 8
Author(s): A. Rodacka, J. Strumillo, E. Serafin and M. Puchala
Affiliation:
Keywords: GAPDH, antioxidant, resveratrol, tiron, protein damage, superoxide anion radical.
Abstract: Protein damage mediated by oxidation has been associated with aging and age-related diseases, in particular neurodegenerative diseases. The protein that is known to be one of the major targets of oxidative stress is glyceraldehyde- 3-phosphate dehydrogenase. GAPDH is believed to play a key role in certain neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. Several recent studies have suggested that a wide range of variety of polyphenols including resveratrol may have neuroprotective effects. Here, we present data that clearly indicate the prooxidative properties of resveratrol and tiron in the inactivation of GAPDH induced by the superoxide anion generated via xanthine oxidase mediated oxidation of xanthine. Generated in the studied system tiron and resveratrol radicals are much more efficient in the inactivation of GAPDH than the superoxide anion alone. The analysis of CD spectra of protein exposed to the tiron and resveratrol radicals revealed little effect on the secondary structure of GAPDH. In both cases reduction of α-helical structure was followed by the increase in β-sheet conformation. Thus, the most probable mechanism of inactivation of GAPDH in the studied system is oxidation of cysteine residues in the catalytic center of the enzyme. Finally, molecular modeling of the resveratrol - GAPDH and tiron - GAPDH complexes showed potential binding sites for those antioxidants with binding affinity -45 kcal/mol and -48 kcal/mol respectively.
Export Options
About this article
Cite this article as:
Rodacka A., Strumillo J., Serafin E. and Puchala M., Effect of Resveratrol and Tiron on the Inactivation of Glyceraldehyde-3- phosphate Dehydrogenase Induced by Superoxide Anion Radical, Current Medicinal Chemistry 2014; 21 (8) . https://dx.doi.org/10.2174/09298673113206660274
DOI https://dx.doi.org/10.2174/09298673113206660274 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Chitosan Nano-encapsulation Enhances Gedunin Cytotoxicity A gainst Human Non-small-cell Lung Cancer (NCI-H292) Cell Line
Drug Delivery Letters Anti-Proliferative, Anti-Inflammatory, Anti-Ulcerogenic and Wound Healing Properties of Chitosan
Current Bioactive Compounds Multidrug Resistance: Retrospect and Prospects in Anti-Cancer Drug Treatment
Current Medicinal Chemistry STAT-3 Inhibitors: State of the Art and New Horizons for Cancer Treatment
Current Medicinal Chemistry Quinazolines as Apoptosis Inducers and Inhibitors: A Review of Patent Literature
Recent Patents on Anti-Cancer Drug Discovery Amplified Crosstalk Between Estrogen Binding and GFR Signaling Mediated Pathways of ER Activation Drives Responses in Tumors Treated with Endocrine Disruptors
Recent Patents on Anti-Cancer Drug Discovery Site-related Effects of Relaxin in the Gastrointestinal Tract Through Nitric Oxide Signalling: An Updated Report
Current Protein & Peptide Science Assessing Cardiovascular Risk in Patients with Diabetes: An Update
Current Cardiology Reviews Fructooligosaccharides of Edible Alliums: Occurrence, Chemistry and Health Benefits
Current Nutrition & Food Science Elevated O-GlcNAcylation Promotes Malignant Phenotypes of Hypopharyngeal Squamous Cell Carcinoma by Stabilizing Nrf2 through Regulation of the PI3K/Akt Pathway
Anti-Cancer Agents in Medicinal Chemistry Small Molecules with EGFR-TK Inhibitor Activity
Current Drug Targets Gas1 is a Pleiotropic Regulator of Cellular Functions: from Embryonic Development to Molecular Actions in Cancer Gene Therapy
Mini-Reviews in Medicinal Chemistry Molecular Signatures of Biomarkers in Cancer Development, Diagn osis, and its Prognostic Accuracy
Current Biomarkers (Discontinued) Recent Patents on Light Based Therapies: Photodynamic Therapy, Photothermal Therapy and Photoimmunotherapy
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Recent Patents on Heat Shock Proteins Targeting Antibodies
Recent Patents on Anti-Cancer Drug Discovery Antibody Engineering for Targeted Therapy of Cancer Recombinant Fv-Immunotoxins
Current Pharmaceutical Biotechnology Chemosensitization by Antisense Oligonucleotides Targeting MDM2
Current Cancer Drug Targets Drug Discovery: Methods for Identifying New Drug Targets
Drug Design Reviews - Online (Discontinued) Efalizumab
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Radiotracers in Oncology
Current Radiopharmaceuticals