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Inhibition of histone deacetylase 3 protects Beta cells from cytokine-induced apoptosis.

Publication TypeJournal Article
AuthorsChou, DH, Holson EB, Wagner FF, Tang AJ, Maglathlin RL, Lewis TA, Schreiber SL, and Wagner BK
AbstractCytokine-induced beta-cell apoptosis is important to the etiology of type-1 diabetes. Although previous reports have shown that general inhibitors of histone deacetylase (HDAC) activity, such as suberoylanilide hydroxamic acid and trichostatin A, can partially prevent beta-cell death, they do not fully restore beta-cell function. To understand HDAC isoform selectivity in beta cells, we measured the cellular effects of 11 structurally diverse HDAC inhibitors on cytokine-induced apoptosis in the rat INS-1E cell line. All 11 compounds restored ATP levels and reduced nitrite secretion. However, caspase-3 activity was reduced only by MS-275 and CI-994, both of which target HDAC1, 2, and 3. Importantly, both MS-275 and genetic knockdown of Hdac3 alone were sufficient to restore glucose-stimulated insulin secretion in the presence of cytokines. These results suggest that HDAC3-selective inhibitors may be effective in preventing cytokine-induced beta-cell apoptosis.
Year of Publication2012
JournalChemistry & biology
Volume19
Issue6
Pages669-73
Date Published (YYYY/MM/DD)2012/06/22
ISSN Number1074-5521
DOI10.1016/j.chembiol.2012.05.010
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/22726680?dopt=Abstract