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Deciphering the mechanism of HNE-induced apoptosis in cultured murine cortical neurons:Transcriptional responses and cellular pathways
journal contribution
posted on 2023-05-17, 01:43 authored by Peng, ZF, Koh, CH, Manikandan, J, Melendez, A, Li, QT, Halliwell, B, Cheung, NSStudies have shown that the lipid peroxidation by-product, 4-hydroxynonenal (HNE), is involved in many pathological events in several neurodegenerative diseases. A number of signaling pathways mediating HNE-induced cell death in the brain have been proposed. However, the exact mechanism remains unknown. In the present study, we have examined the effects of HNE on cultured primary cortical neurons and found that HNE treatment leads to cell death via apoptosis. Both the caspase and calpain proteolytic systems were activated. There were also increased levels of phospho-p53 and cell cycle-related proteins. Gene transcription was further studied using microarray analysis. Results showed that majority of the genes associated with cell cycle regulation, response to stress, and signal transduction were differentially expressed. The various categories of differentially-expressed genes suggested that there are other parallel pathways regulating HNE-induced neuronal apoptosis. Collectively, these might help to elucidate similar molecular mechanisms involved during cell death in neurodegenerative diseases.
History
Publication title
NeuropharmacologyVolume
53Issue
5Pagination
687-698ISSN
0028-3908Department/School
Menzies Institute for Medical ResearchPublisher
Pergamon-Elsevier Science LtdPlace of publication
The Boulevard, Langford Lane, Kidlington, Oxford, England, Ox5 1GbRepository Status
- Restricted