Biomaterial Database

Histone deacetylase inhibitors: a new mode for inhibition of cholesterol metabolism. 2008

Sridar V Chittur, and Niquiche Sangster-Guity, and Paulette J McCormick

Center for Functional Genomics, University at Albany, State University of New York, Cancer Research Center, One Discovery Drive, Rm 310, Rensselaer, NY 12144, USA. schittur@albany.edu

BACKGROUND Eukaryotic gene expression is a complex process involving multiple cis and trans activating molecules to either facilitate or inhibit transcription. In recent years, many studies have focused on the role of acetylation of histone proteins in modulating transcription, whereas deacetylation of these same proteins is associated with inactivation or repression of gene expression. This study explores gene expression in HepG2 and F9 cell lines treated with Trichostatin A (TSA), a potent histone deacetylase inhibitor. RESULTS These experiments show that TSA treatment results in clear repression of genes involved in the cholesterol biosynthetic pathway as well as other associated pathways including fatty acid biosynthesis and glycolysis. TSA down regulates 9 of 15 genes in this pathway in the F9 embryonal carcinoma model and 11 of 15 pathway genes in the HepG2 cell line. A time course study on the effect of TSA on gene expression of various enzymes and transcription factors involved in these pathways suggests that down regulation of Srebf2 may be the triggering factor for down regulation of the cholesterol biosynthesis pathway. CONCLUSIONS Our results provide new insights in the effects of histone deacetylases on genes involved in primary metabolism. This observation suggests that TSA, and other related histone deacetylase inhibitors, may be useful as potential therapeutic entities for the control of cholesterol levels in humans.

UI	MeSH Term	Description	Entries
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D002784	Cholesterol	The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.	Epicholesterol
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006877	Hydroxamic Acids	A class of weak acids with the general formula R-CONHOH.	Hydroxamic Acid,Acid, Hydroxamic,Acids, Hydroxamic
D000107	Acetylation	Formation of an acetyl derivative. (Stedman, 25th ed)	Acetylations
D000924	Anticholesteremic Agents	Substances used to lower plasma CHOLESTEROL levels.	Cholesterol Inhibitors,Hypocholesteremic Agents,Anticholesteremic Drugs,Anticholesteremics,Inhibitors, Cholesterol,Agents, Anticholesteremic,Agents, Hypocholesteremic,Drugs, Anticholesteremic
D051782	Sterol Regulatory Element Binding Protein 2	A sterol regulatory element binding protein that regulates GENES involved in CHOLESTEROL synthesis and uptake.	SRE-2 Binding Protein,SREBP2 Protein,Sterol-Regulatory Element-Binding Protein 2,SRE 2 Binding Protein
D053858	Metabolic Networks and Pathways	Complex sets of enzymatic reactions connected to each other via their product and substrate metabolites.	Metabolic Networks,Metabolic Pathways,Metabolic Network,Metabolic Pathway,Network, Metabolic,Networks, Metabolic,Pathway, Metabolic,Pathways, Metabolic