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Hydrogen peroxide induces neurite degeneration: Prevention by tocotrienols
Koji Fukui1, Hirokatsu Takatsu, Tatsuro Koike
1Physiological Chemistry Laboratory, Department of Bioscience and Engineering, College of Systems Engineering and Sciences, Shibaura Institute of Technology,Fukasaku 307, Minuma-ku, Saitama, 337-8570, Japan. koji@sic.shibaura-it.ac.jp
Abstract:
Reactive oxygen species (ROS) may attack several types of tissues and chronic exposure to ROS may attenuate various biological functions and increase the risk of several types of serious disorders. It is known that treatments with ROS attack neurons and induce cell death. However, the mechanisms of neuronal change by ROS prior to induction of cell death are not yet understood. Here, it was found that treatment of neurons with low concentrations of hydrogen peroxide induced neurite injury, but not cell death. Unusual bands located above the original collapsin response mediator protein (CRMP)-2 protein were detected by western blotting. Treatment with tocopherol or tocotrienols significantly inhibited these changes in neuro2a cells and cerebellar granule neurons (CGCs). Furthermore, prevention by tocotrienols of hydrogen peroxide-induced neurite degeneration was stronger than that by tocopherol. These findings indicate that neurite beading is one of the early events of neuronal degeneration prior to induction of death of hydrogen peroxide-treated neurons. Treatment with tocotrienols may protect neurite function through its neuroprotective function.
Insights
Hydrogen peroxide causes early neurite beading in neurons, a sign of degeneration before cell death. Tocotrienols effectively prevent this damage, offering neuroprotection.
Area of Science:
- Neuroscience
- Biochemistry
- Toxicology
Background:
- Reactive oxygen species (ROS) can damage tissues, including neurons, potentially leading to cell death.
- The precise mechanisms of early neuronal changes induced by ROS before cell death remain unclear.
Purpose of the Study:
- To investigate the early molecular mechanisms of neuronal injury induced by hydrogen peroxide (H2O2).
- To evaluate the protective effects of tocopherol and tocotrienols against H2O2-induced neuronal damage.
Main Methods:
- Neuronal cell cultures (neuro2a and cerebellar granule neurons) were treated with low concentrations of H2O2.
- Western blotting was used to detect changes in collapsin response mediator protein (CRMP)-2.
- The effects of tocopherol and tocotrienols on H2O2-induced changes were assessed.
Main Results:
- H2O2 treatment induced neurite injury, characterized by beading, without causing cell death.
- Unusual higher molecular weight bands of CRMP-2 were observed after H2O2 treatment.
- Tocopherol and tocotrienols inhibited these H2O2-induced CRMP-2 alterations.
- Tocotrienols demonstrated a stronger protective effect against H2O2-induced neurite degeneration than tocopherol.
Conclusions:
- Neurite beading is an early indicator of neuronal degeneration caused by H2O2 exposure.
- Tocotrienols exhibit significant neuroprotective properties by preventing H2O2-induced neurite damage.
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