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Simplified apoptotic cascades

Heart Failure Reviews volume 13, pages 111–119 (2008)Cite this article

Abstract

Apoptosis is an evolutionarily conserved mode of cell death that is tightly regulated and critical for multicellular organism development and cellular homeostasis. Specific biochemical and morphological changes characterise cells undergoing apoptosis, and reflect the specificity in which activated apoptotic pathways follow. The two best-characterized apoptotic pathways are the extrinsic pathway and the intrinsic pathway, which involve cell surface death receptors and the mitochondria and endoplasmic reticulum respectively. Apoptotic stimuli lead to activation of either or both of these pathways, and involve sequential activation of different cysteine proteases (caspases), and in the case of the intrinsic pathway, activation of a family of Bcl-2 proteins that critically regulate cell death. Conversely, dis-inhibition of endogenous inhibitors is often required for effective apoptotic cell death. Furthermore, an interesting recurring protein-protein interaction within this framework of apoptotic cascades involves interactions between death domain motifs that are present on many of the regulatory proteins in both apoptotic pathways. Cardiomyocyte apoptosis has been demonstrated in human heart failure and in rodents, apoptosis itself directly causes dilated cardiomyopathy. Understanding the intricacies of apoptotic death pathways and determining the relevance of these to cardiomyopathy is therefore essential if cardiomyocyte apoptosis is to be a pharmacological target for heart failure therapy.

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Acknowledgement

R.S-Y.Foo is supported by a Wellcome Trust Advanced Fellowship. MM is supported by a project grant from the British Heart Foundation to RSYF and Professor Martin Bennett (Cambridge).

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  1. Division of Cardiovascular Medicine, Addenbrooke’s Hospital, University of Cambridge, ACCI Building Level 6, Hills Road, Box 110, Cambridge, CB2 2QQ, UK

    Mehregan Movassagh & Roger S.-Y. Foo

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  1. Mehregan Movassagh
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Correspondence to Roger S.-Y. Foo.

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Movassagh, M., Foo, R.SY. Simplified apoptotic cascades. Heart Fail Rev 13, 111–119 (2008). https://doi.org/10.1007/s10741-007-9070-x

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Keywords

  • Cardiomyocyte
  • Apoptosis
  • Death domains
  • Caspases