Gene profiling reveals hydrogen sulphide recruits death signaling via the N-methyl-D-aspartate receptor identifying commonalities with excitotoxicity
Data(s) |
01/05/2011
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Resumo |
Recently the role of hydrogen sulphide (H<sub>2</sub>S) 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 H<sub>2</sub>S-mediated dose- and time-dependent injury. Moreover N-methyl-D-aspartate receptor (NMDAR) antagonists abolished the consequences of H<sub>2</sub>S-induced neuronal death. This study focuses on deciphering the downstream effects activation of NMDAR on H<sub>2</sub>S-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 200 µM 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 H<sub>2</sub>S 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 H<sub>2</sub>S-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 H<sub>2</sub>S neuropathologies where NMDAR-activated signaling cascades played a substantial role. J. Cell. Physiol. 226: 1308–1322, 2011. |
Identificador | |
Idioma(s) |
eng |
Publicador |
John Wiley & Sons |
Relação |
http://dro.deakin.edu.au/eserv/DU:30040514/li-geneprofiling-2011.pdf http://dx.doi.org/10.1002/jcp.22459 |
Direitos |
2010, Wiley-Liss, Inc. |
Tipo |
Journal Article |