© 2004 American Heart Association, Inc.
Letters to the Editor |
Heat Shock–Related Protein 20 (HSP20) in Cardiomyocytes
Harrington Department of Bioengineering and Arizona, Biodesign Institute, Arizona State University, Tempe, Ariz, and, Carl T. Hayden Veteran’s Affairs Medical Center, Phoenix, Ariz, colleen.brophy{at}asu.edu
To the Editor:
In the article, "Phosphoproteome analysis of cardiomyocytes subjected to ß-adrenergic stimulation," Chu et al concluded that "a de novo phosphorylation of a cardiac heat shock protein p20 was identified, for the first time, in mouse cardiomyocytes, after prolonged activation of the ß-adrenergic signaling pathway.1 However, cyclic nucleotide-dependent phosphorylation of p20, also referred to as heat shock-related protein 20 (HSP20), has been well characterized in smooth, skeletal, and cardiac muscles.2 The phosphorylation on serine 16 has also been described.3 Thus, the novelty of this report by Chu et al is limited to the animal model (mouse) and the modality of stimulation (ß-adrenergic).
Chu et al used adenoviral transfection of p20 to determine the functional relevance of the protein. They suggested that transfection of p20 leads to "increased cell contractility and intracellular calcium transients amplitudes." Our group used a different approach, that of transiently permeabililzing rat cardiomyocytes and treating the cells with phosphopeptide analogues of p20 to elucidate the function of this molecule.2 The phosphopeptide analogue, but not scrambled peptide controls, led to an increased rate of contractility because of a more rapid relaxation time. We found no change in the amplitude of the calcium transient; however, there was a more rapid rate of decay of the calcium transient. Chu et al did not indicate what the transfection efficiency was, nor did they provide any information on changes in p20 expression or phosphorylation after transfection. Without this information, it is difficult to compare and contrast the differing results.
More recently, we have used protein transduction domains to carry phosphopeptide analogues across the cell membrane of smooth muscle. Transduction of a 13-amino acid peptide that contains the sequence surrounding the serine 16, with a phosphoserine, leads to smooth muscle relaxation.4 These data raise the possibility that direct manipulation of the phosphoproteome may open avenues to new approaches for drug discovery and development.
We agree that an increasing body of literature suggests that cyclic nucleotide-dependent phosphorylation of p20 has a role in muscle function. A more inclusive approach to the extant literature might lead to a more comprehensive understanding of the role this molecule plays in muscle tissues.
References
- Chu G, Egnaczyk GF, Zhao W, Jo SH, Fan GC, Maggio JE, Xiao RP, Kranias EG. Phosphoproteome analysis of cardiomyocytes subjected to beta-adrenergic stimulation: identification and characterization of a cardiac heat shock protein p20. Circ Res. 2004; 94: 184–193.
[Abstract/Free Full Text] - Pipkin W, Johnson JA, Creazzo TL, Burch J, Komalavilas P, Brophy C. Localization, Macromolecular Associations, and Function of the Small Heat Shock-Related Protein HSP20 in Rat Heart. Circulation. 2003; 107: 469–476.
[Abstract/Free Full Text] - Beall A, Bagwell D, Woodrum DA, Stoming TA, Kato K, Suzuki A, Rasmussen H, Brophy CM. The small heat shock-related protein, HSP20, is phosphorylated on serine 16 during cyclic nucleotide-dependent relaxation. J Biol Chem. 1999; 274: 11344–11351.
[Abstract/Free Full Text] - Flynn CR, Komalavilas P, Tessier D, Thresher J, Niederkofler EE, Dreiza CM, Nelson RW, Panitch A, Joshi L, Brophy CM. Transduction of biologically active motifs of the small heat shock- related protein, HSP20, leads to relaxation of vascular smooth muscle. FASEB J. 2003; 10: 1358–1360.
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