Deciphering the mechanism of HNE-induced apoptosis in cultured murine cortical neurons: transcriptional responses and cellular pathways.
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.
Peng
Zhao Feng
ZF
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
Koh
Chor Hui Vivien
CH
Li
Qiu Tian
QT
Manikandan
Jayapal
J
Melendez
Alirio J
AJ
Tang
Soon Yew
SY
Halliwell
Barry
B
Cheung
Nam Sang
NS
D000111:Acetylcysteine / Q000494:pharmacology; D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002154:Calpain / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D003599:Cytoskeleton / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology; D016158:Genes, p53; D051379:Mice; D046228:Microarray Analysis; D009474:Neurons / Q000187:drug effects*; D018384:Oxidative Stress / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D025801:Ubiquitin / Q000502:physiology
D000447:Aldehydes; D018797:Cell Cycle Proteins; D016166:Free Radical Scavengers; D025801:Ubiquitin; D002154:Calpain; D020169:Caspases; C027576:4-hydroxy-2-nonenal; D000111:Acetylcysteine