Deciphering the mechanism of HNE-induced apoptosis in cultured murine cortical neurons: Transcriptional responses and cellular pathways

Cheung, N. S., Halliwell, B., Koh, C. H. V., Li, Q. T., Manikandan, J., Melendez, A. J., Peng, Z. F. and Tang, S. Y. (2007) Deciphering the mechanism of HNE-induced apoptosis in cultured murine cortical neurons: Transcriptional responses and cellular pathways. Neuropharmacology, 53(5), pp. 687-698. (doi:10.1016/j.neuropharm.2007.07.016)

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Publisher's URL: http://dx.doi.org/10.1016/j.neuropharm.2007.07.016

Abstract

Studies 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Halliwell, Prof Barry and Melendez Romero, Dr Alirio
Authors: Cheung, N. S., Halliwell, B., Koh, C. H. V., Li, Q. T., Manikandan, J., Melendez, A. J., Peng, Z. F., and Tang, S. Y.
College/School:College of Medical Veterinary and Life Sciences
Journal Name:Neuropharmacology
Publisher:Elsevier
ISSN:0028-3908
ISSN (Online):1873-7064
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
462311Therapeutic potential of Sphingosine Kinase blockage in allergic anaphylaxis.Alirio Melendez RomeroMedical Research Council (MRC)G0700794Institute of Infection Immunity and Inflammation