Temporal transcriptomic profiling reveals cellular targets that govern survival in HOCl-mediated neuronal apoptosis.
OBJECTIVE
With the identification of hypochlorous acid (HOCl) as a biomarker in diseased brains and endogenous detection of its modified proteins, HOCl might be implicated in the development of neurodegenerative disorders. However, its effect on neuronal cell death has not yet been investigated at gene expression level.


METHODS
Therefore, DNA microarray was performed for screening of HOCl-responsive genes in primary mouse cortical neurons. Neurotoxicity caused by physiological relevant HOCl (250μM) exhibited several biochemical markers of apoptosis.


RESULTS
The biological processes affected during HOCl-mediated apoptosis included cell death, response to stress, cellular metabolism, and cell cycle. Among them, mRNAs level of cell death and stress response genes were up-regulated while expression of metabolism and cell cycle genes were down-regulated.


CONCLUSIONS
Our results showed, for the first time, that HOCl induces apoptosis in cortical neurons by upregulating apoptotic genes and gene expression of stress response such as heat shock proteins and antioxidant proteins were enhanced to provide protection. These data form a foundation for the development of screening platforms and define targets for intervention in HOCl neuropathologies where HOCl-mediated injury is causative.
Yap
Yann Wan
YW
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
Chen
Minghui Jessica
MJ
Choy
Meng Shyan
MS
Peng
Zhao Feng
ZF
Whiteman
Matthew
M
Manikandan
Jayapal
J
Melendez
Alirio J
AJ
Cheung
Nam Sang
NS
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D002453:Cell Cycle; D002478:Cells, Cultured; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006997:Hypochlorous Acid / Q000378:metabolism* / Q000633:toxicity; D051379:Mice; D019579:Neocortex / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000503:physiopathology; D009474:Neurons / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
D015415:Biomarkers; D012333:RNA, Messenger; D006997:Hypochlorous Acid