Edwards, H. V., Scott, J. D. and Baillie, G. S. (2012) PKA phosphorylation of the small heat-shock protein Hsp20 enhances its cardioprotective effects. Biochemical Society Transactions, 40(1), pp. 210-214. (doi: 10.1042/BST20110673)
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Publisher's URL: http://dx.doi.org/10.1042/BST20110673
Abstract
The small heat-shock protein Hsp20 (heat-shock protein 20), also known as HspB6, has been shown to protect against a number of pathophysiological cardiac processes, including hypertrophy and apoptosis. Following β-adrenergic stimulation and local increases in cAMP, Hsp20 is phosphorylated on Ser<sup>16</sup> by PKA (protein kinase A). This covalent modification is required for many of its cardioprotective effects. Both Hsp20 expression levels and its phosphorylation on Ser<sup>16</sup> are increased in ischaemic myocardium. Transgenic mouse models with cardiac-specific overexpression of Hsp20 that are subject to ischaemia/reperfusion show smaller myocardial infarcts, and improved recovery of contractile performance during the reperfusion phase, compared with wild-type mice. This has been attributed to Hsp20's ability to protect against cardiomyocyte necrosis and apoptosis. Phosphomimics of Hsp20 (S16D mutants) confer improved protection from β-agonist-induced apoptosis in the heart, whereas phospho-null mutants (S16A) provide no protection. Naturally occurring mutants of Hsp20 at position 20 (P20L substitution) are associated with markedly reduced Hsp20 phosphorylation at Ser<sup>16</sup>, and this lack of phosphorylation correlates with abrogation of Hsp20's cardioprotective effects. Therefore phosphorylation of Hsp20 at Ser<sup>16</sup> by PKA is vital for the cardioprotective actions of this small heat-shock protein. Selective targeting of signalling elements that can enhance this modification represents an exciting new therapeutic avenue for the prevention and treatment of myocardial remodelling and ischaemic injury.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Baillie, Professor George and Edwards, Dr Helen |
| Authors: | Edwards, H. V., Scott, J. D., and Baillie, G. S. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Biochemical Society Transactions |
| Publisher: | Portland Press Ltd. |
| ISSN: | 0300-5127 |
| ISSN (Online): | 1470-8752 |
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