Temporal transcriptomic profiling reveals cellular targets that govern survival in HOCl-mediated neuronal apoptosis

Yap, Y.W., Chen, M.J., Choy, M.S., Peng, Z.F., Whiteman, M., Manikandan, J., Melendez Romero, A.J. and Cheung, N.S. (2010) Temporal transcriptomic profiling reveals cellular targets that govern survival in HOCl-mediated neuronal apoptosis. Life Sciences, 87(15-16), pp. 457-467. (doi:10.1016/j.lfs.2010.08.011)

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Publisher's URL: http://dx.doi.org/10.1016/j.lfs.2010.08.011

Abstract

Aims: 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Melendez Romero, Dr Alirio
Authors: Yap, Y.W., Chen, M.J., Choy, M.S., Peng, Z.F., Whiteman, M., Manikandan, J., Melendez Romero, A.J., and Cheung, N.S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Life Sciences
ISSN:0024-3205
ISSN (Online):1879-0631
Published Online:15 September 2010

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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