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Gene Profiling Reveals Hydrogen Sulphide Recruits Death Signaling via the N-Methyl-D Aspartate Receptor Identifying Commonalities With Excitotoxicity
Citation
Chen, MJ and Peng, ZF and Manikandan, J and Melendez, AJ and Tan, GS and Chung, CM and Li, QT and Tan, TM and Deng, LW and Whiteman, M and Beart, PM and Moore, PK and Cheung, NS, Gene Profiling Reveals Hydrogen Sulphide Recruits Death Signaling via the N-Methyl-D Aspartate Receptor Identifying Commonalities With Excitotoxicity, Journal of Cellular Physiology, 226, (5) pp. 1308-1322. ISSN 0021-9541 (2011) [Refereed Article]
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Abstract
Recently the role of hydrogen sulphide (H2S) as a gasotransmitter stimulated wide interest owing to its involvement in Alzheimer’s disease
and ischemic stroke. Previously we demonstrated the importance of functional ionotropic glutamate receptors (GluRs) by neurons is
critical for H2S-mediated dose- and time-dependent injury. Moreover N-methyl-D-aspartate receptor (NMDAR) antagonists abolished
the consequences of H2S-induced neuronal death. This study focuses on deciphering the downstream effects activation of NMDAR
on H2S-mediated neuronal injury by analyzing the time-course of global gene profiling (5, 15, and 24 h) to provide a comprehensive
description of the recruitment of NMDAR-mediated signaling. Microarray analyses were performed on RNA from cultured mouse
primary cortical neurons treated with 200mM sodium hydrosulphide (NaHS) or NMDA over a time-course of 5–24 h. Data were
validated via real-time PCR, western blotting, and global proteomic analysis. A substantial overlap of 1649 genes, accounting for over 80%
of NMDA global gene profile present in that of H2S and over 50% vice versa, was observed. Within these commonly occurring genes, the
percentage of transcriptional consistency at each time-point ranged from 81 to 97%. Gene families involved included those related to cell death, endoplasmic reticulum stress, calcium homeostasis, cell cycle, heat shock proteins, and chaperones. Examination of genes exclusive
to H2S-mediated injury (43%) revealed extensive dysfunction of the ubiquitin-proteasome system. These data form a foundation for the
development of screening platforms and define targets for intervention in H2S neuropathologies where NMDAR-activated signaling
cascades played a substantial role.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Neurosciences |
| Research Field: | Cellular nervous system |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Chen, MJ (Ms Minghui Chen) |
| UTAS Author: | Cheung, NS (Dr Nam Cheung) |
| ID Code: | 69780 |
| Year Published: | 2011 |
| Web of Science® Times Cited: | 24 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2011-05-18 |
| Last Modified: | 2012-03-19 |
| Downloads: | 0 |
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