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Temporal transcriptomic profiling reveals cellular targets that govern survival in HOCl-mediated neuronal apoptosis
journal contribution
posted on 2023-05-17, 06:30 authored by Yap, YW, Chen, Minghui Jessica, Choy, MS, Peng, ZF, Whiteman, M, Manikandan, J, Melendez, AJ, Cheung, NSAims: 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. Main methods: Therefore, DNA microarray was performed for screening of HOCl-responsive genes in primary mouse cortical neurons. Neurotoxicity caused by physiological relevant HOCl (250 μM) exhibited several biochemical markers of apoptosis. Key findings: 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. Significance: 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.
History
Publication title
Life SciencesVolume
87Issue
15-16Pagination
457-467ISSN
0024-3205Department/School
Menzies Institute for Medical ResearchPublisher
Pergamon-Elsevier Science LtdPlace of publication
United StatesRepository Status
- Restricted