Cell signaling and neurotoxicity: protein kinase C in vitro and in vivo
1Neurotoxicology Branch, National Health and Environmental Effects Research Laboratories, United States Environmental Protection Agency, Research Triangle Park, NC, USA. kodavanti.prasada@epa.gov
Abstract:
There is a growing concern about the effects of chemicals on the developing nervous system. Chemical exposure at critical periods of development can be associated with effects ranging from subtle to profound on the structure and/or function of the nervous system. Understanding critical biological molecular targets, which underlie chemical-induced neurotoxicity, will provide a scientific basis for risk assessment. Cell signaling molecules such as protein kinase C (PKC) have been shown to play critical roles in motor activity, development of the nervous system, and in learning and memory. PKC also has been shown to be associated with several neurological disorders including Alzheimer's disease, status epilepticus, and cerebellar ataxia. In the literature, there is abundant information linking PKC to cognitive function, long-term potentiation, or brain structural changes. Here, we show the relationship between changes in PKC (as assayed using radioactive material or by western blots) and the neurotoxic effects caused by environmental chemicals in vitro and in vivo.
Insights
Environmental chemicals can harm the developing nervous system. This study links changes in protein kinase C (PKC) to chemical-induced neurotoxicity, aiding risk assessment.
Area of Science:
- Neuroscience
- Toxicology
- Molecular Biology
Background:
- Growing concerns exist regarding the impact of chemical exposure on the developing nervous system.
- Chemicals can cause subtle to profound neurodevelopmental effects.
- Identifying molecular targets of neurotoxicity is crucial for risk assessment.
Purpose of the Study:
- To investigate the relationship between changes in protein kinase C (PKC) and neurotoxic effects from environmental chemicals.
- To establish a scientific basis for assessing the risks of chemical-induced neurodevelopmental toxicity.
Main Methods:
- Assaying protein kinase C (PKC) activity using radioactive material.
- Utilizing western blots to quantify PKC levels.
- Conducting in vitro and in vivo experiments to assess neurotoxicity.
Main Results:
- Demonstrated a correlation between altered PKC levels and neurotoxic outcomes.
- Provided evidence for PKC as a molecular target in chemical-induced neurotoxicity.
- Established a link between environmental chemical exposure and changes in PKC signaling.
Conclusions:
- Protein kinase C (PKC) is a key molecular player in neurodevelopmental toxicity.
- Understanding PKC alterations aids in evaluating the neurotoxic potential of environmental chemicals.
- This research supports the development of improved neurotoxicity risk assessments.
More Related Videos
Related Concept Videos
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
02:54Protein Kinases and Phosphatases
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
01:22Amplifying Signals via Enzymatic Cascade
01:16Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:24Intracellular Signaling Cascades
01:07MAPK Signaling Cascades