Related Experiment Video
Updated: Jul 19, 2026
Protocol for Culturing Sympathetic Neurons from Rat Superior Cervical Ganglia (SCG)
Published on: January 30, 2009
Differential effect of nerve growth factor on dopaminergic neurotoxin-induced apoptosis
Yoko Hirata1, Tomotaka Meguro, Kazutoshi Kiuchi
1Department of Biomolecular Science, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193, Japan. yoko@biomol.gifu-u.ac.jp
Abstract:
Both rotenone and manganese are possible neurotoxins for a wide variety of cell and neuronal types including dopaminergic neurons and induce apoptosis in various cells. Neurotrophic factors have the potential for therapeutic development when used to prevent Parkinson's disease. In this paper, we focused on the differences between rotenone and manganese as toxins, and characterized the influence of neurotrophic factors on toxin-induced apoptosis in PC12 cells. There were distinct differences in intracellular mechanisms between rotenone- and manganese-induced apoptosis such as the production of reactive oxygen species, the response to antioxidants, and the activation of the c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). Nerve growth factor (NGF) almost completely prevented rotenone-induced but not manganese-induced caspase activation and DNA fragmentation. The differential effect of NGF was found to be mainly due to the down-regulation of the Trk tyrosine kinase receptor by manganese but not by rotenone. Prevention of rotenone-induced apoptosis by NGF was attenuated by the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, LY294002, but not MAPK kinase (MEK) inhibitors, PD98059 or U0126. These results demonstrate that the potential neurotoxins for dopaminergic cells exert their toxic effect by activation of different signaling pathways of apoptosis and that NGF prevents rotenone-induced apoptosis through the activation of the PI 3-kinase pathway not MAPK pathway.
Insights
Rotenone and manganese induce apoptosis via distinct pathways. Nerve growth factor (NGF) protects against rotenone-induced cell death by activating the PI 3-kinase pathway, but not manganese-induced apoptosis.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- Rotenone and manganese are neurotoxins implicated in dopaminergic neuron damage.
- Neurotrophic factors show therapeutic potential for neurodegenerative diseases like Parkinson's disease.
- Understanding toxin-specific mechanisms is crucial for developing effective treatments.
Purpose of the Study:
- To differentiate the intracellular mechanisms of rotenone- and manganese-induced apoptosis.
- To investigate the neuroprotective effects of neurotrophic factors on these toxins.
- To elucidate the signaling pathways involved in toxin-induced apoptosis and neuroprotection.
Main Methods:
- PC12 cells were treated with rotenone or manganese to induce apoptosis.
- Cellular responses including reactive oxygen species production and kinase activation were analyzed.
- The effect of Nerve Growth Factor (NGF) on apoptosis and its underlying signaling pathways (PI 3-kinase, MAPK) was assessed using specific inhibitors.
Main Results:
- Rotenone and manganese induced apoptosis through different intracellular mechanisms, including varying reactive oxygen species production and kinase activation (JNK, p38 MAPK).
- NGF significantly inhibited rotenone-induced caspase activation and DNA fragmentation, but not manganese-induced apoptosis.
- Manganese, unlike rotenone, down-regulated the Trk tyrosine kinase receptor, contributing to NGF's differential effect.
- NGF's protective effect against rotenone was mediated by the phosphatidylinositol 3-kinase (PI 3-kinase) pathway, not the MAPK pathway.
Conclusions:
- Rotenone and manganese activate distinct apoptotic signaling pathways in dopaminergic cells.
- NGF demonstrates neuroprotective potential against rotenone-induced apoptosis via the PI 3-kinase pathway.
- These findings highlight the importance of pathway-specific therapeutic strategies for neuroprotection.
More Related Videos
09:02Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing
Published on: June 9, 2017
15:05Functional Evaluation of Biological Neurotoxins in Networked Cultures of Stem Cell-derived Central Nervous System Neurons
Published on: February 5, 2015
