Abstract
In the mouse postoperative ileus model, we have shown an increase in oxidative stress after intestinal manipulation occurring earlier in the mucosa than in the muscular layer, which might contribute to epithelial barrier dysfunction. To address these findings in vitro, we assessed TNF-α/cycloheximide (CHX)-induced oxidative stress and apoptosis in a mouse intestinal epithelial cell line, MODE-K. The influence of heme oxygenase (HO)-1-related products and agents known to reduce reactive oxygen species (ROS) production on TNF-α/CHX-induced oxidative stress and apoptosis were investigated. MODE-K cells were exposed to different concentrations of TNF- α/CHX in the absence/presence of the test agents. Cell viability, caspase-3/7 activity, apoptosis, reduced glutathione level (GSH) and intracellular ROS production were measured. TNF-α/CHX decreased cell viability, increased caspase-3/7 activity, induced apoptosis, reduced the GSH level and increased ROS production in a concentration-dependent manner in MODE-K cells. All these effects of TNF- α/CHX were partially prevented by pretreatment with a carbon monoxide-releasing agent (CORM-A1) and nitrite. The antioxidant resveratrol abolished TNF-α/CHX-induced increase in ROS production and caspase-3/7 activity, but apoptosis was only partially prevented. MODE-K cells are sensitive to TNF-α-induced apoptosis in the presence of CHX, which is associated with increased intracellular ROS production and caspase-3/7 activation. The effects were partially mitigated by CORM-A1, nitrite and resveratrol. Thus, these agents could be of potential use in protecting the epithelial barrier against oxidative stress during intestinal ischemia/reperfusion injury.
Keywords: MODE-K cells, TNF-α/CHX, ROS, apoptosis, bilirubin, CORM-A1, nitrite, resveratrol, oxidative stress, ischemia/reperfusion injury
Current Pharmaceutical Design
Title:TNF-α/Cycloheximide-Induced Oxidative Stress and Apoptosis in Murine Intestinal Epithelial MODE-K Cells
Volume: 18 Issue: 28
Author(s): Dinesh Babu, Stefaan J. Soenen, Koen Raemdonck, Georges Leclercq, Ole De Backer, Roberto Motterlini and Romain A. Lefebvre
Affiliation:
Keywords: MODE-K cells, TNF-α/CHX, ROS, apoptosis, bilirubin, CORM-A1, nitrite, resveratrol, oxidative stress, ischemia/reperfusion injury
Abstract: In the mouse postoperative ileus model, we have shown an increase in oxidative stress after intestinal manipulation occurring earlier in the mucosa than in the muscular layer, which might contribute to epithelial barrier dysfunction. To address these findings in vitro, we assessed TNF-α/cycloheximide (CHX)-induced oxidative stress and apoptosis in a mouse intestinal epithelial cell line, MODE-K. The influence of heme oxygenase (HO)-1-related products and agents known to reduce reactive oxygen species (ROS) production on TNF-α/CHX-induced oxidative stress and apoptosis were investigated. MODE-K cells were exposed to different concentrations of TNF- α/CHX in the absence/presence of the test agents. Cell viability, caspase-3/7 activity, apoptosis, reduced glutathione level (GSH) and intracellular ROS production were measured. TNF-α/CHX decreased cell viability, increased caspase-3/7 activity, induced apoptosis, reduced the GSH level and increased ROS production in a concentration-dependent manner in MODE-K cells. All these effects of TNF- α/CHX were partially prevented by pretreatment with a carbon monoxide-releasing agent (CORM-A1) and nitrite. The antioxidant resveratrol abolished TNF-α/CHX-induced increase in ROS production and caspase-3/7 activity, but apoptosis was only partially prevented. MODE-K cells are sensitive to TNF-α-induced apoptosis in the presence of CHX, which is associated with increased intracellular ROS production and caspase-3/7 activation. The effects were partially mitigated by CORM-A1, nitrite and resveratrol. Thus, these agents could be of potential use in protecting the epithelial barrier against oxidative stress during intestinal ischemia/reperfusion injury.
Export Options
About this article
Cite this article as:
Babu Dinesh, J. Soenen Stefaan, Raemdonck Koen, Leclercq Georges, De Backer Ole, Motterlini Roberto and A. Lefebvre Romain, TNF-α/Cycloheximide-Induced Oxidative Stress and Apoptosis in Murine Intestinal Epithelial MODE-K Cells, Current Pharmaceutical Design 2012; 18 (28) . https://dx.doi.org/10.2174/138161212802481291
DOI https://dx.doi.org/10.2174/138161212802481291 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read 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
-
Dendritic Cell Immunotherapy for Malignant Gliomas
Reviews on Recent Clinical Trials Pharmacological Characteristics and Clinical Applications of K201
Current Clinical Pharmacology New Sides of Aldosterone Action in Cardiovascular System as Potential Targets for Therapeutic Intervention
Current Drug Targets Peroxisome Proliferator-Activated Receptors: The Nutritionally Controlled Molecular Networks that Integrate Inflammation, Immunity and Metabolism
Current Nutrition & Food Science Screening of NO Inhibitor Release Activity from Soft Coral Extracts Origin Palu Bay, Central Sulawesi, Indonesia
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Neurotrophic and Neuroprotective Effects of Muscle Contraction
Current Pharmaceutical Design Potential Non-neoplastic Applications for Polyphenols in Stem Cell Utilization
Current Drug Targets Effect of Aging on Metabolic Pathways in Endothelial Progenitor Cells
Current Pharmaceutical Design Targets Involved in Cardioprotection by the Non-Anesthetic Noble Gas Helium
Current Drug Targets Targeting of Nuclear Factor-κB and Proteasome by Dithiocarbamate Complexes with Metals
Current Pharmaceutical Design Modulation of Cellular Response to Anticancer Treatment by Caffeine: Inhibition of Cell Cycle Checkpoints, DNA Repair and More
Current Pharmaceutical Biotechnology Role of Nitric Oxide Signaling Pathways in Brain Injuries
Current Chemical Biology Antioxidant Properties and Medicinal Uses of Some Crataegus Spp. (Hawthorn) Including <i>C. meyeri</i> and <i>C. pontica</i>
Current Nutrition & Food Science Remote Ischemic Conditioning Improves Cognitive Function During Cerebral Vascular Injury Through the Induction of Autophagy
Current Neurovascular Research Editorial [Hot topic: Crucial Role of Redox Signaling in the Regulation of Heart Health (Guest Editor: Dipak K. Das)]
Current Cardiology Reviews New Insights in Research About Acute Ischemic Myocardial Injury and Inflammation
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Structure-based Pharmacophore Clustering of Multi- Conformation Proteins: Application to Identify Novel and Diverse CypD Inhibitors
Current Proteomics Circulating Biomarkers Determining Inflammation in Atherosclerosis Progression
Current Medicinal Chemistry Statins Attenuate Fibrotic Manifestations of Cardiac Tissue Damage
Current Molecular Pharmacology Subject Index to Volume 1
Current Neurovascular Research