Insights into the Sigma-1 receptor Chaperone's cellular functions: A microarray report
Version of Record online: 11 OCT 2011
Copyright © 2011 Wiley Periodicals, Inc.
Volume 66, Issue 1, pages 42–51, January 2012
How to Cite
Tsai, S.-Y., Rothman, R. K. and Su, T.-P. (2012), Insights into the Sigma-1 receptor Chaperone's cellular functions: A microarray report. Synapse, 66: 42–51. doi: 10.1002/syn.20984
- Issue online: 18 NOV 2011
- Version of Record online: 11 OCT 2011
- Accepted manuscript online: 9 SEP 2011 05:38AM EST
- Manuscript Accepted: 24 AUG 2011
- Manuscript Received: 20 APR 2011
- Intramural Research Program
- National Institute on Drug Abuse, NIH/DHHS
- sigma receptor;
We previously demonstrated that Sig-1Rs are critical regulators in neuronal morphogenesis and development via the regulation of oxidative stress and mitochondrial functions. In the present study, we sought to identify pathways and genes that are affected by Sig-1R. Gene expression profiles were examined in rat hippocampal neurons that had been cultured for 18 days in vitro (DIV). The cells were transduced with AAV siRNA targeting Sig-1R on DIV 10 for 7 days, followed by gene expression analysis using a rat genome cDNA array. The gene array results indicated that Sig-1R knockdown hampered cellular functions including steroid biogenesis, protein ubiquitination, actin cytoskeleton network, and Nrf-2 mediated oxidative stress. Many of the cellular components important for actin polymerization and synapse plasticity, including F-actin capping protein and neurofilaments, were significantly changed in AAV-siSig-1R neurons. Further, cytochrome c was reduced in AAV-Sig-1R neurons whereas free-radical generating enzymes including cytochrome p450 and cytochrome b-245 were increased. The microarray results also suggest that Sig-1Rs may regulate genes that are involved in the pathogenesis of many CNS diseases including Alzheimer's disease and Parkinson's disease. These data further confirmed that Sig-1Rs play critical roles in the CNS and thus these findings may aid in future development of therapeutic treatments targeting neurodegenerative disorders. Synapse, 2012. © 2011 Wiley Periodicals, Inc.