title: Selective regulation of class I and class II histone deacetylases expression by inhibitors of histone deacetylases in cultured mouse neural cells.
abstract: The expression of 10 histone deacetylases (HDAC1-10) mRNAs in mouse neuroblastoma Neuro-2a and microglia N9 cell cultures after treatment by inhibitors of HDACs, sodium butyrate and trichostatin A was studied to elucidate whether HDAC inhibitors affect the gene expression of HDACs themselves. Northern blot analysis demonstrated two- to four-fold elevated levels of mRNAs for HDAC1, -3, -5, and -6 after drug treatment in comparison with untreated cells, while mRNA levels for HDAC2 and -7 did not change significantly. In both Neuro-2a and N9 cells the highest increase was observed for HDAC5 and -6 mRNA, whereas, HDAC4 had a prominent increase in mRNA levels after drug treatment only in N9 microglia cell line but not in Neuro-2a. Immunocytochemical examination confirmed that changes in protein levels of HDACs were similar to changes in their mRNA levels. There exists an auto-regulatory feedback loop to the expression levels of several HDACs after inhibition of their biochemical activity, adding several HDAC genes to the list of genes regulated by HDAC inhibitors.
authors.affiliation: Department of Neurobiology, A.I. Virtanen Institute for Molecular Science, University of Kuopio, P.O. Box 1627 (Neulaniementie 2), FIN 70211 Kuopio, Finland.
authors.forename: Farzam
authors.initials: F
authors.lastname: Ajamian
authors.forename: Antero
authors.initials: A
authors.lastname: Salminen
authors.forename: Mati
authors.initials: M
authors.lastname: Reeben
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D007150:Immunohistochemistry; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000201:enzymology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics
chemical_list: D004791:Enzyme Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C484389:Hdac1 protein, mouse; C533424:Hdac2 protein, mouse; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases