HDAC4 Regulates Neuronal Survival in Normal and Diseased Retinas

被引：165

作者：

Chen, Bo ^{[1
,2
,3
]}

Cepko, Constance L. ^{[1
,2
,3
]}

机构：

[1] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA

来源：

SCIENCE | 2009年 / 323卷 / 5911期

关键词：

CONTROLS CHONDROCYTE HYPERTROPHY; MEF2 TRANSCRIPTION FACTOR; CELL-DEATH; INTRACELLULAR TRAFFICKING; RETINITIS-PIGMENTOSA; BETA-SUBUNIT; MOUSE; PHOSPHODIESTERASE; DIFFERENTIATION; DEGENERATION;

D O I：

10.1126/science.1166226

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Histone deacetylase 4 ( HDAC4) shuttles between the nucleus and cytoplasm and serves as a nuclear co- repressor that regulates bone and muscle development. We report that HDAC4 regulates the survival of retinal neurons in the mouse in normal and pathological conditions. Reduction in HDAC4 expression during normal retinal development led to apoptosis of rod photoreceptors and bipolar ( BP) interneurons, whereas overexpression reduced naturally occurring cell death of the BP cells. HDAC4 overexpression in a mouse model of retinal degeneration prolonged photoreceptor survival. The survival effect was due to the activity of HDAC4 in the cytoplasm and relied at least partly on the activity of hypoxia- inducible factor 1 alpha (HIF1 alpha). These data provide evidence that HDAC4 plays an important role in promoting the survival of retinal neurons.

引用

页码：256 / 259

页数：4

共 22 条

[1] MEF2C transcription factor controls chondrocyte hypertrophy and bone development [J].