The small heat shock proteins Hsp20 and αB-crystallin in cultured cardiac myocytes: differences in cellular localization and solubilization after heat stress

Klundert, Francy A. J. M. van de; Jong, Wilfried W. de

doi:10.1016/s0171-9335(99)80022-3

Cited by 28 publications

(16 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34 However, under heat stress, Hsp20 has been reported to migrate partially into the nucleus, with very few cells displaying a faint sarcomeric association of Hsp20. 35 These results suggest that Hsp20 redistributes from the soluble to the insoluble nuclear/cytoskeletal fraction in response to the stress state of the cell. Therefore, it is possible that the relocalization of Hsp20 may be protective for the collapsed intermediate filament network or cytoskeletal protein damage, induced by stress stimulation.…”

Section: Discussionmentioning

confidence: 87%

Small Heat-Shock Protein Hsp20 Phosphorylation Inhibits β-Agonist-Induced Cardiac Apoptosis

Fan

Chu

Mitton

et al. 2004

Circulation Research

112

144

View full text Add to dashboard Cite

Abstract-Activation of the sympathetic nervous system is a common compensatory feature in heart failure, but sustained ␤-adrenergic activation induces cardiomyocyte death, leading to cardiac remodeling and dysfunction. In mouse cardiomyocytes, we recently reported that prolonged exposure to ␤-agonists is associated with transient increases in expression and phosphorylation of a small heat-shock protein, Hsp20. To determine the functional significance of Hsp20, we overexpressed this protein and its constitutively phosphorylated (S16D) or nonphosphorylated (S16A) mutant in adult rat cardiomyocytes. Hsp20 protected cardiomyocytes from apoptosis triggered by activation of the cAMP-PKA pathway, as indicated by decreases in the number of pyknotic nuclei, terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling, and DNA laddering, which were associated with inhibition of caspase-3 activity. These protective effects were further increased by the constitutively phosphorylated Hsp20 mutant (S16D), which conferred full protection from apoptosis. In contrast, the nonphosphorylatable mutant (S16A) exhibited no antiapoptotic properties. Immunostaining studies and immunoprecipitations with Hsp20 or actin antibodies demonstrated that Hsp20 translocated to cytoskeleton and associated with actin on isoproterenol stimulation. These findings suggest that Hsp20 and its phosphorylation at Ser16 may provide cardioprotection against ␤-agonist-induced apoptosis. Thus, Hsp20 may represent a novel therapeutic target in the treatment of heart failure.

show abstract

Section: Discussionmentioning

confidence: 87%

Small Heat-Shock Protein Hsp20 Phosphorylation Inhibits β-Agonist-Induced Cardiac Apoptosis

Fan

Chu

Mitton

et al. 2004

Circulation Research

112

144

View full text Add to dashboard Cite

show abstract

“…In contrast, complete removal of the amino-terminal domain, including the putative nuclear localization signal, resulted in nuclear translocation. One interpretation of this finding is that decreased oligomer disassembly permits p26 movement through nuclear pores by simple diffusion, and nuclear translocation of rat Hsp20 and Hsp25 upon heat shock, where they may play protective roles, is accompanied by stress-induced decrease in oligomer mass, perhaps to dimers for Hsp20 (59). However, p26, reduced in oligomer size because of carboxyl-terminal truncation, remained in the cytoplasm, suggesting that simple diffusion is not occurring.…”

Section: Table III Oligomerization Of P26 Synthesized In Transfected mentioning

confidence: 98%

Oligomerization, Chaperone Activity, and Nuclear Localization of p26, a Small Heat Shock Protein from Artemia franciscana

Sun

Mansour

Crack

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Artemia franciscana embryos undergo encystment, developmental arrest and diapause, the last characterized by profound metabolic dormancy and extreme stress resistance. Encysted embryos contain an abundant small heat shock protein termed p26, a molecular chaperone that undoubtedly has an important role in development. To understand better the role of p26 in Artemia embryos, the structural and functional characteristics of full-length and truncated p26 expressed in Escherichia coli and COS-1 cells were determined. p26 chaperone activity declined with increasing truncation of the protein, and those deletions with the greatest adverse effect on protection of citrate synthase during thermal stress had the most influence on oligomerization. When produced in either prokaryotic or eukaryotic cells the p26 ␣-crystallin domain consisting of amino acid residues 61-152 existed predominantly as monomers, and p26 variants lacking the amino-terminal domain but with intact carboxyl-terminal extensions were mainly monomers and dimers. The amino terminus was, therefore, required for efficient dimer formation. Assembly of higher order oligomers was enhanced by the carboxyl-terminal extension, although removing the 10 carboxyl-terminal residues had relatively little effect on oligomerization and chaperoning. Full-length and carboxyl-terminal truncated p26 resided in the cytoplasm of transfected COS-1 cells; however, variants missing the complete amino-terminal domain and existing predominantly as monomers/dimers entered the nuclei. A mechanism whereby oligomer disassembly assisted entry of p26 into nuclei was suggested, this of importance because p26 translocates into Artemia embryo nuclei during development and stress. However, when examined in Artemia, the p26 oligomer size was unchanged under conditions that allowed movement into nuclei, suggesting a process more complex than just oligomer dissociation.The small heat shock proteins (sHsps), 1 characterized by a conserved ␣-crystallin domain exhibiting an immunoglobulinlike fold bordered by variable amino-and carboxyl-terminal extensions (1-7), function as molecular chaperones. The molecular mass of sHsps ranges from 12 to 43 kDa, and most oligomerize by a multistep process often with dimers as stable suboligomeric units (8, 9), although for bovine ␣B-crystallin monomers may be basic building blocks (10). For sHsps such as Hsp20 (11) and Hsp22 (12), dimers are the predominant complex, and they exhibit chaperone activity. Of medical significance, ␣A-crystallin truncations occur in mammalian lens, suggesting a relationship between carboxyl-terminal modification and cataract (13,14). Also, dropping either 13 or 25 carboxylterminal residues from human ␣B-crystallin causes myofibrillar myopathy, with modified proteins exerting dominant negative effects (15). The truncated and normal ␣B-crystallins appear to interact, yielding oligomers slightly smaller than those generated by wild type protein.Assembly mechanisms and the resulting oligomers vary for sHsps from different sources (2, 4,...

show abstract

“…For MKBP and HSP25 an increase of these proteins has been reported in the myofibrillar protein pool after ischemia of isolated rat hearts (Yoshida et al 1999). Immunostaining for HSP20 of cultured cardiomyocytes exposed to heat shock also revealed a faint sarcomeric staining pattern indicative of myofibrillar translocation of HSP20 (van de Klundert and de Jong 1999). Localization of the other sHSPs upon stress conditions has so far not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the small heat shock proteins ?B-crystallin, MKBP, HSP25, HSP20, and cvHSP in heart and skeletal muscle

Golenhofen

Perng

Quinlan

et al. 2000

Histochem Cell Biol

155

160

View full text Add to dashboard Cite

Seven members of the small heat shock protein (sHSP) family are exceptional with respect to their constitutive high abundance in muscle tissue. It has been suggested that sHSPs displaying chaperone-like properties may stabilize myofibrillar proteins during stress conditions and prevent them from loss of function. In the present study five sHSPs (alphaB-crystallin, MKBP, HSP25, HSP20, and cvHSP) were investigated with respect to similarities and differences of their expression in heart and skeletal muscle under normal and ischemic conditions. In ischemic heart and skeletal muscle these five sHSPs translocated from cytosol to the Z-/I-area of myofibrils. Myofibrillar binding of all sHSPs was very tight and resisted for the most part extraction with 1 M NaSCN or 1 M urea. MKBP and HSP20 became extracted by 1 M NaSCN to a significant extent indicating that these two sHSPs may bind partially to actin-associated proteins which were completely extracted by this treatment. Ultrastructural localization of alphaB-crystallin showed diffuse distribution of immunogold label throughout the entire I-band in skeletal muscle fibers whereas in cardiomyocytes alphaB-crystallin was preferentially located at the N-line position of the I-band. These observations indicate different myofibrillar binding sites of alphaB-crystallin in cardiomyocytes versus skeletal muscle fibers. Further differences of the properties of sHSPs could be observed regarding fiber type distribution of sHSPs. Thus sHSPs form a complex stress-response system in striated muscle tissue with some common as well as some distinct functions in different muscle types.

show abstract

The small heat shock proteins Hsp20 and αB-crystallin in cultured cardiac myocytes: differences in cellular localization and solubilization after heat stress

Cited by 28 publications

References 40 publications

Small Heat-Shock Protein Hsp20 Phosphorylation Inhibits β-Agonist-Induced Cardiac Apoptosis

Small Heat-Shock Protein Hsp20 Phosphorylation Inhibits β-Agonist-Induced Cardiac Apoptosis

Oligomerization, Chaperone Activity, and Nuclear Localization of p26, a Small Heat Shock Protein from Artemia franciscana

Comparison of the small heat shock proteins ?B-crystallin, MKBP, HSP25, HSP20, and cvHSP in heart and skeletal muscle

Contact Info

Product

Resources

About