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Differential Effects of CORM-2 and CORM-401 in Murine Intestinal Epithelial MODE-K Cells under Oxidative Stress
- Source :
- Frontiers in Pharmacology, FRONTIERS IN PHARMACOLOGY
- Publication Year :
- 2017
- Publisher :
- Frontiers Media S.A., 2017.
-
Abstract
- Carbon monoxide (CO)-releasing molecules (CO-RMs) are intensively studied to provide cytoprotective and anti-inflammatory effects of CO in inflammatory conditions including intestinal inflammation. The water-soluble CORM-A1 reduced apoptosis and NADPH oxidase (NOX)-derived reactive oxygen species (ROS) induced by tumor necrosis factor (TNF)-alpha/cycloheximide (CHX) in mouse MODE-K intestinal epithelial cells (IECs), without influencing TNF-alpha/CHX-induced mitochondrial superoxide anion (O-2(center dot-)). The aim of the present study in the same model was to comparatively investigate the influence of lipid-soluble CORM-2 and water-soluble CORM-401, shown in vitro to release more CO under oxidative conditions. CORM-2 abolished TNF-alpha/CHX-induced total cellular ROS whereas CORM-401 partially reduced it, both partially reducing TNF-alpha/CHXinduced cell death. Only CORM-2 increased mitochondrial O-2(center dot-) production after 2 h of incubation. CORM-2 reduced TNF-alpha/CHX-, rotenone-and antimycin-A-induced mitochondrial O-2(center dot-) production; CORM-401 only reduced the effect of antimycin-A. Co-treatment with CORM-401 during 1 h exposure to H2O2 reduced H2O2 (7.5 mM)induced ROS production and cell death, whereas CORM-2 did not. The study illustrates the importance of the chemical characteristics of different CO-RMs. The lipid solubility of CORM-2 might contribute to its interference with TNF-alpha/CHX-induced mitochondrial ROS signaling, at least in mouse IECs. CORM-401 is more effective than other CO-RMs under H2O2-induced oxidative stress conditions.
- Subjects :
- 0301 basic medicine
Mitochondrial ROS
Programmed cell death
SUPEROXIDE ANION
SPECIES FORMATION
hydrogen peroxide
Oxidative phosphorylation
Mitochondrion
medicine.disease_cause
MONOXIDE-RELEASING MOLECULES
03 medical and health sciences
0302 clinical medicine
HYDROGEN-PEROXIDE PRODUCTION
medicine
TNF-α/CHX
oxidative stress
Pharmacology (medical)
CARBON-MONOXIDE
HEME OXYGENASE
IN-VIVO
Original Research
chemistry.chemical_classification
Pharmacology
reactive oxygen species
Reactive oxygen species
NADPH oxidase
biology
TNF-alpha/CHX
carbon monoxide-releasing molecules
solubility
Biology and Life Sciences
Carbon monoxide-releasing molecules
Cell biology
mitochondria
030104 developmental biology
chemistry
Biochemistry
ULCERATIVE-COLITIS
030220 oncology & carcinogenesis
THERAPEUTIC APPLICATIONS
biology.protein
intestinal epithelial cells
CO-RMS
Oxidative stress
Subjects
Details
- Language :
- English
- ISSN :
- 16639812
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Frontiers in Pharmacology
- Accession number :
- edsair.doi.dedup.....953a9b8af1d7d68b2bb59296d023561b