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Morphine induces apoptosis of human endothelial cells through nitric oxide and reactive oxygen species pathways
- Source :
- Toxicology. 256:83-91
- Publication Year :
- 2009
- Publisher :
- Elsevier BV, 2009.
-
Abstract
- Morphine has been widely used for pain management. Other than analgesia, it has effects on vascular endothelial cells, including angiogenesis and apoptosis. An in vitro model of human umbilical vein endothelial cells (HUVECs) was made to investigate the effects and comprehensive mechanisms of morphine on vascular endothelial cells. Morphine enhanced apoptosis of HUVECs, increased intracellular reactive oxygen species (ROS), and reduced mitochondrial membrane potentials (MMPs). It also induced the release of NO and activated NF-κB in HUVECs. Naloxone, the opioid receptor antagonist, could reverse cell apoptosis and ROS generation, NO production, and MMP loss. Expression levels of Bak and Bax, and the activation of caspases 3 and 7 in HUVECs significantly increased when treated with morphine. Inhibition of NO production by NO synthase inhibitor reduced morphine-induced apoptosis. Morphine could induce apoptosis of HUVECs through both the NO and ROS pathways. Thus, inhibiting NO or ROS may be a potential target in blocking morphine-induced apoptosis of endothelial cells.
- Subjects :
- Programmed cell death
Cell Survival
Angiogenesis
Blotting, Western
Apoptosis
(+)-Naloxone
Biology
Nitric Oxide
Toxicology
medicine.disease_cause
Cell Line
Membrane Potentials
Nitric oxide
chemistry.chemical_compound
medicine
Humans
Immunoprecipitation
Caspase 7
chemistry.chemical_classification
Reactive oxygen species
Dose-Response Relationship, Drug
Morphine
Caspase 3
NF-kappa B
Endothelial Cells
Hydrogen Peroxide
Flow Cytometry
Cell biology
Analgesics, Opioid
Endothelial stem cell
chemistry
Mitochondrial Membranes
Immunology
Reactive Oxygen Species
Oxidative stress
Subjects
Details
- ISSN :
- 0300483X
- Volume :
- 256
- Database :
- OpenAIRE
- Journal :
- Toxicology
- Accession number :
- edsair.doi.dedup.....c828c3bda8b4488bc79dfbe27b0319d9