Identification of novel targets for PGC-1{alpha} and histone deacetylase inhibitors in neuroblastoma cells
Journal Article
·
· Biochemical and Biophysical Research Communications
- Department of Psychiatry, University of Alabama, Birmingham, AL 35294 (United States)
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109 (United States)
Recent evidence suggests that the transcriptional coactivator peroxisome proliferator activated receptor {gamma} coactivator 1{alpha} (PGC-1{alpha}) is involved in the pathology of Huntington's Disease (HD). While animals lacking PGC-1{alpha} express lower levels of genes involved in antioxidant defense and oxidative phosphorylation in the brain, little is known about other targets for PGC-1{alpha} in neuronal cells and whether there are ways to pharmacologically target PGC-1{alpha} in neurons. Here, PGC-1{alpha} overexpression in SH-SY5Y neuroblastoma cells upregulated expression of genes involved in mitochondrial function, glucose transport, fatty acid metabolism, and synaptic function. Overexpression also decreased vulnerability to hydrogen peroxide-induced cell death and caspase 3 activation. Treatment of cells with the histone deacetylase inhibitors (HDACi's) trichostatin A and valproic acid upregulated PGC-1{alpha} and glucose transporter 4 (GLUT4). These results suggest that PGC-1{alpha} regulates multiple pathways in neurons and that HDACi's may be good candidates to target PGC-1{alpha} and GLUT4 in HD and other neurological disorders.
- OSTI ID:
- 21255875
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 379; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
Similar Records
Histone deacetylase inhibitors epigenetically promote reparative events in primary dental pulp cells
Complex molecular mechanisms cooperate to mediate histone deacetylase inhibitors anti-tumour activity in neuroblastoma cells
Gene expression profiling in response to the histone deacetylase inhibitor BL1521 in neuroblastoma
Journal Article
·
Mon Jun 10 00:00:00 EDT 2013
· Experimental Cell Research
·
OSTI ID:22267812
Complex molecular mechanisms cooperate to mediate histone deacetylase inhibitors anti-tumour activity in neuroblastoma cells
Journal Article
·
Wed Jun 11 20:00:00 EDT 2008
· Molecular Cancer
·
OSTI ID:1626575
Gene expression profiling in response to the histone deacetylase inhibitor BL1521 in neuroblastoma
Journal Article
·
Sat Oct 01 00:00:00 EDT 2005
· Experimental Cell Research
·
OSTI ID:20717664