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Neurodegenerative, with expression ATF-2 by p38 in cortical neurons
M Hosseini1, N Ostad, K Parivar
1Department of Science, Islamshahr Branch, Islamic Azad University, Tehran, Iran.
Abstract:
DNA damage, as an important initiator of neuronal cell death, has been implicated in numerous neurodegenerative conditions. We previously delineated several pathways that control embryonic cortical neuronal cell death evoked by the DNA-damaging agent, camptothecin. The topisomerase-1 inhibitor, camptothecin, has been shown to induce cortical neuronal cell death in a reproducible and synchronistic manner. Primary embryonic neuronal cell culture cortical neurons were prepared. In the study, the survival % of neurons in camptothecin P38 group, after 6 hours (85%), 24 hours (64%) and 48 hours (50%), compared to camptothecin ATF-2 and P38 group after 4 hours (97 and 95%), have been significantly lower, and the expression % of neurons in camptothecin P38 group , after 6 hours (20%), 24 hours (40%) and 48 hours (55%), compared to camptothecin ATF-2 and P38 group after 4 hours (5 and 3%) have been significant lower (p<0.05). The expression % of neurons in camptothecin P38 group, after 24 hours (40%), compared to camptothecin ATF-2 group after 24hours (30%), have been significant lower (p<0.05). This study revealed that camptothecin induces P38 expression and P38 in embryonic cortical neurons to determine the importance of the P38 pathway in neuronal death following DNA damage, and P38 is induce phosphorylation of ATF-2 in embryonic cortical neurons following DNA damage.
Insights
DNA damage triggers neuronal cell death, impacting neurodegenerative diseases. This study reveals camptothecin induces P38 expression and ATF-2 phosphorylation in embryonic cortical neurons, highlighting the P38 pathway
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- DNA damage is a key factor in neurodegenerative diseases, initiating neuronal cell death.
- Previous research identified pathways regulating embryonic cortical neuronal cell death induced by DNA-damaging agents.
- Camptothecin, a topoisomerase-1 inhibitor, consistently induces cortical neuronal cell death.
Purpose of the Study:
- To investigate the role of the P38 pathway in neuronal death following DNA damage.
- To determine if camptothecin induces P38 expression and ATF-2 phosphorylation in embryonic cortical neurons.
Main Methods:
- Primary embryonic neuronal cell cultures were prepared.
- Cortical neurons were treated with camptothecin.
- Neuronal survival and P38 expression were quantified at various time points.
Main Results:
- Camptothecin treatment significantly reduced neuronal survival in the P38 group compared to controls.
- Camptothecin significantly increased P38 expression in a time-dependent manner.
- P38 pathway activation was linked to increased phosphorylation of ATF-2 in response to DNA damage.
Conclusions:
- Camptothecin induces P38 expression and subsequent ATF-2 phosphorylation in embryonic cortical neurons.
- The P38 pathway plays a critical role in mediating neuronal cell death after DNA damage.
- Findings elucidate a key molecular mechanism underlying DNA damage-induced neurodegeneration.
