HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Wallace, D. M. Articles by Cotter, T. G. Search for Related Content PubMed PubMed Citation Articles by Wallace, D. M. Articles by Cotter, T. G.

Histone Deacetylase Activity Regulates Apaf-1 and Caspase 3 Expression in the Developing Mouse Retina

From the Cell Development and Disease Laboratory, Department of Biochemistry, Biosciences Institute, University College Cork, Cork, Ireland.

PURPOSE. Apoptosis is a form of programmed cell death essential for both tissue development and maintenance of tissue homeostasis. Apoptosis protease activating factor (Apaf)-1 and caspase 3 are downregulated in the retina during postnatal development. The decreased expression of these genes is potentially a critical survival strategy adopted to protect against accidental cell death. The purpose of this study was to investigate the transcriptional mechanism involved in the downregulation of Apaf-1 and caspase 3.

METHODS. SDS-polyacrylamide gel electrophoresis and semiquantitative PCR were used to examine Apaf-1 and caspase 3 expression levels during development. TdT-mediated dUTP nick-end labeling (TUNEL) and DNA laddering were used to identify cells undergoing apoptosis.

RESULTS. A decrease in expression of Apaf-1 and caspase 3 during retinal development correlated with a decreased susceptibility to an apoptotic stimulus. Furthermore, treatment with a histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), resulted in widespread hyperacetylation in the retina, coinciding with transcriptional activation of Apaf-1 and caspase 3 and subsequent induction of apoptosis in postnatal day (P)5 and P15 retinas. However, inhibition of HDAC activity is not sufficient to induce apoptosis in the mature retina (P60).

CONCLUSIONS. Overall, these results elicit the conclusion that downregulation of Apaf-1 and caspase 3 in the developing retina correlates with a decreased susceptibility to apoptotic stimuli and ensures the survival of the retina. Furthermore, the authors propose that, in the early postnatal retina, HDAC activity governs the transcriptional regulation of these genes. Upregulation of Apaf-1 and caspase 3 coincides with an induction of apoptosis. In the mature retina transcriptional activation of these genes or induction of apoptosis was not observed.

This article has been cited by other articles:

				J. C. Walker and R. M. Harland microRNA-24a is required to repress apoptosis in the developing neural retina Genes & Dev., May 1, 2009; 23(9): 1046 - 1051. [Abstract] [Full Text] [PDF]

				K. M. Wright, M. I. Smith, L. Farrag, and M. Deshmukh Chromatin modification of Apaf-1 restricts the apoptotic pathway in mature neurons J. Cell Biol., December 3, 2007; 179(5): 825 - 832. [Abstract] [Full Text] [PDF]