期刊
CELL DEATH & DISEASE
卷 1, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2010.4
关键词
epigenetic; neuroprotection; trichostatin A; retina; sirtuin; retinitis pigmentosa
类别
资金
- EU [MRTN-CT-2003-504003, LSHG-CT-2005-512036, MEST-CT-2005-020235]
- Fundacion Oftalmologica del Mediterraneo (FOM)
- KMA
- Synframjandets Forskningsfond
- Stiftelsen for synskadade i f.d. Malmohus lan
- Foundation Fighting Blindness (FFB)
- Swedish Medical Research Council (VRM)
- Crafoord foundation
- Kerstan Foundation
- Torsten och Ragnar Soderbergs Foundation
- Deutsche Forschungsgemeinschaft (DFG) [PA1751/1-1]
Inherited retinal degenerations, collectively termed retinitis pigmentosa (RP), constitute one of the leading causes of blindness in the developed world. RP is at present untreatable and the underlying neurodegenerative mechanisms are unknown, even though the genetic causes are often established. Acetylation and deacetylation of histones, carried out by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively, affects cellular division, differentiation, death and survival. We found acetylation of histones and probably other proteins to be dramatically reduced in degenerating photoreceptors in the rd1 human homologous mouse model for RP. Using a custom developed in situ HDAC activity assay, we show that overactivation of HDAC classes I/II temporally precedes photoreceptor degeneration. Moreover, pharmacological inhibition of HDACs I/II activity in rd1 organotypic retinal explants decreased activity of poly-ADP-ribose-polymerase and strongly reduced photoreceptor cell death. These findings highlight the importance of protein acetylation for photoreceptor cell death and survival and propose certain HDAC classes as novel targets for the pharmacological intervention in RP. Cell Death and Disease (2010) 1, e24; doi:10.1038/cddis.2010.4; published online 11 February 2010
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