Expression patterns of histone deacetylases in experimental stroke and potential targets for neuroprotection
Article first published online: 28 AUG 2012
© 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd
Clinical and Experimental Pharmacology and Physiology
Volume 39, Issue 9, pages 751–758, September 2012
How to Cite
Chen, Y.-T., Zang, X.-F., Pan, J., Zhu, X.-L., Chen, F., Chen, Z.-B. and Xu, Y. (2012), Expression patterns of histone deacetylases in experimental stroke and potential targets for neuroprotection. Clinical and Experimental Pharmacology and Physiology, 39: 751–758. doi: 10.1111/j.1440-1681.2012.05729.x
- Issue published online: 28 AUG 2012
- Article first published online: 28 AUG 2012
- Accepted manuscript online: 1 JUN 2012 05:16AM EST
- Manuscript Accepted: 28 MAY 2012
- Manuscript Revised: 14 MAY 2012
- Manuscript Received: 31 JAN 2012
- National Natural Science Foundation of China. Grant Numbers: 30971010, 30670739
- Outstanding Researcher Program. Grant Number: RC2007006
- National Natural Science Foundation . Grant Number: BK2009037
- Ministry of Science and Technology in China . Grant Number: CB521906
- Science and Technology Achievement Transformation Foundation of Jiangsu Province. Grant Number: BA2009124
- Postgraduate Innovation Project of Nanjing University. Grant Number: CL03
- histone deacetylase;
- Histone deacetylase (HDAC) inhibitors exert neuroprotection in both cellular and animal models of ischaemic stroke. However, which HDAC isoform (or isoforms) mediates this beneficial effect has not yet been determined.
- In the present study, gene levels of the HDAC isoforms were determined in the mouse cortex using reverse transcription–polymerase chain reaction (RT-PCR), whereas changes in the expression of individual zinc-dependent HDAC family members were evaluated by western blotting, 3, 12, 24 and 48 h after cerebral ischaemia induced by transient middle cerebral artery occlusion in male Kunming mice.
- The HDAC isoforms HDAC1–11 were all expressed in the mouse cortex and differentially affected by cerebral ischaemia. Notably, there was a substantial increase in HDAC3, HDAC6 and HDAC11 expression during the early phases of experimental stroke, indicating their contribution to stroke pathogenesis. Furthermore, induction of HDAC3 and HDAC6 in cortical neurons by ischaemic stroke was confirmed in vivo and in vitro using double-labelled immunostaining and RT-PCR, respectively. Therefore, small hairpin (sh) RNAs were used to selectively knock down HDAC3 or HDAC6. This knockdown appreciably promoted the survival of cortical neurons subjected to oxygen and glucose deprivation.
- The findings of the present study demonstrate the expression patterns of HDAC isoforms during experimental ischaemic stroke. Furthermore, HDAC3 and HDAC6 were identified as potential mediators in the neurotoxicity of ischaemic stroke, suggesting that specific therapeutic approaches may be considered according to HDAC subtype.