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Apoptosis as a specific biomarker of diazinon toxicity in NTera2-D1 cells
M G Aluigi1, C Guida, C Falugi
1Dipartimento di Biologia (DIBIO), Università di Genova, Viale Benedetto XV, No. 5, I-16132 Genova, Italy.
Abstract:
The NTera2/D1 (NT2) cell line, which was derived from a human teratocarcinoma, exhibits properties that are characteristics of a committed neuronal precursor at an early stage of differentiation. Its property to express a whole set of molecules related to the cholinergic neurotransmission system, including active acetylcholinesterase (AChE, EC 3.1.1.7) makes it a good alternative model for testing the effects of neurotoxic compounds, such as organophosphorus (OP) insecticides, whose primary target is the inhibition of AChE activity. Recent findings have elucidated the role of AChE in the modulation of apoptosis, but the mechanisms are still rather obscure. NT2 cells exposed to the OP insecticide diazinon at concentrations ranging between 10(-4) and 10(-5)M showed a time-dependent enhancement of cell death. When exposed at 10(-6)M diazinon showed higher cell viability than control samples up to 72 h, followed by a decreasing phase. The cell death caused by the exposures showed a number of features characteristic of apoptosis, including membrane and mitochondrial potential changes. We suggest the hypothesis that such behaviour is due to a dynamic balance between activated and blocked acetylcholine receptors that in turn trigger electrical events and caspase cascade.
Insights
Organophosphorus insecticides like diazinon can induce apoptosis in neuronal precursor cells. This cell death is linked to acetylcholinesterase inhibition and altered acetylcholine receptor activity.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- The NTera2/D1 (NT2) cell line, derived from human teratocarcinoma, serves as a model for early neuronal precursor differentiation.
- NT2 cells express cholinergic neurotransmission molecules, including acetylcholinesterase (AChE), making them suitable for studying neurotoxic compounds.
- AChE's role in apoptosis modulation is recognized but not fully understood.
Purpose of the Study:
- To investigate the effects of the organophosphorus insecticide diazinon on NT2 cell viability and apoptosis.
- To explore the potential mechanisms underlying diazinon-induced cell death in this neuronal precursor model.
Main Methods:
- NT2 cells were exposed to varying concentrations of diazinon (10(-4) to 10(-6)M).
- Cell viability and apoptotic features, including membrane and mitochondrial potential changes, were assessed over time.
Main Results:
- Diazinon exposure at 10(-4) and 10(-5)M resulted in time-dependent cell death.
- Lower concentration (10(-6)M) initially increased cell viability before decreasing.
- Observed cell death exhibited characteristics of apoptosis.
Conclusions:
- Diazinon induces apoptosis in NT2 cells, suggesting a neurotoxic effect.
- The findings support a hypothesis involving a balance of acetylcholine receptor activity, electrical events, and caspase activation in diazinon-induced apoptosis.
