Advertisement

Pflügers Archiv

, Volume 451, Issue 4, pp 518–525 | Cite as

Ischemia-induced increase of stiffness of αB-crystallin/HSPB2-deficient myocardium

  • N. Golenhofen
  • A. Redel
  • E. F. Wawrousek
  • D. Drenckhahn
Cardiovascular System

Abstract

The two small heat shock proteins (sHSPs), αB-crystallin and HSPB2, have been shown to translocate within a few minutes of cardiac ischemia from the cytosol to myofibrils; and it has been suggested that their chaperone-like properties might protect myofibrillar proteins from unfolding or aggregation during stress conditions. Further evidence of an important role for HSPs in muscle function is provided by the fact that mutations of the αB-crystallin gene cause myopathy and cardiomyopathy. In the present study, we subjected isolated papillary muscles of αB-crystallin/HSPB2-deficient mice to simulated ischemia and reperfusion. During ischemia in αB-crystallin/HSPB2-deficient muscles, the development of contracture started earlier and reached a higher value compared to the wildtype mice. The recovery of contracture of αB-crystallin/HSPB2-deficient muscles was also attenuated during the simulated reperfusion period. However, twitch force was not significantly altered at any time of the experiment. This suggests that during ischemic insults, αB-crystallin/HSPB2 may not be important for the contraction process itself, but rather serve to maintain muscular elasticity.

Keywords αB-crystallin HSPB2 Stress proteins Titin Ischemia Contractility Mouse papillary muscle Diastolic relaxation 

Notes

Acknowledgements

We are grateful to Heike Arthen for excellent technical assistance. This study was supported by the Deutsche Forschungsgemeinschaft (SFB 355).

References

  1. 1.
    Barbato R, Menabo R, Dainese P, Carafoli E, Schiaffino S, Di Lisa F (1996) Binding of cytosolic proteins to myofibrils in ischemic rat hearts. Circ Res 78:821–828PubMedGoogle Scholar
  2. 2.
    Bennardini F, Wrzosek A, Chiesi M (1992) AlphaB-crystallin in cardiac tissue. Association with actin and desmin filaments. Circ Res 71:288–294Google Scholar
  3. 3.
    Brady JP, Garland DL, Green DE, Tamm ER, Giblin FJ, Wawrousek EF (2001) AlphaB-Crystallin in lens development and muscle integrity: a gene knockout approach. Invest Ophthalmol Vis Sci 42:2924–2934PubMedGoogle Scholar
  4. 4.
    Bullard B, Ferguson C, Minajeva A, Leake MC, Gautel M, Labeit D et al (2004) Association of the chaperone alphaB-crystallin with titin in heart muscle. J Biol Chem 279:7917–7924CrossRefPubMedGoogle Scholar
  5. 5.
    Carmeliet E (1999) Cardiac ionic currents and acute ischemia: from channels to arrhythmias. Physiol Rev 79:917–1017PubMedGoogle Scholar
  6. 6.
    Cazorla O, Freiburg A, Helmes M, Centner T, McNabb M, Wu Y et al (2000) Differential expression of cardiac titin isoforms and modulation of cellular stiffness. Circ Res 86:59–67PubMedGoogle Scholar
  7. 7.
    Chiesi M, Longoni S, Limbruno U (1990) Cardiac alpha-crystallin. III. Involvement during heart ischemia. Mol Cell Biochem 97:129–136Google Scholar
  8. 8.
    de Jong WW, Leunissen JA, Voorter CE (1993) Evolution of the alpha-crystallin/small heat-shock protein family. Mol Biol Evol 10:103–126PubMedGoogle Scholar
  9. 9.
    Erickson HP (1997) Stretching single protein molecules: titin is a weird spring. Science 276:1090–1092CrossRefPubMedGoogle Scholar
  10. 10.
    Freiburg A, Trombitas K, Hell W, Cazorla O, Fougerousse F, Centner T et al (2000) Series of exon-skipping events in the elastic spring region of titin as the structural basis for myofibrillar elastic diversity. Circ Res 86:1114–1121PubMedGoogle Scholar
  11. 11.
    Gerull B, Gramlich M, Atherton J, McNabb M, Trombitas K, Sasse-Klaassen S et al (2002) Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy. Nat Genet 30:201–204CrossRefPubMedGoogle Scholar
  12. 12.
    Golenhofen N, Arbeiter A, Koob R, Drenckhahn D (2002) Ischemia-induced association of the stress protein alphaB-crystallin with I-band portion of cardiac titin. J Mol Cell Cardiol 34:309–319CrossRefPubMedGoogle Scholar
  13. 13.
    Golenhofen N, Perng M, Quinlan RA, Drenckhahn D (2004) Comparison of the small heat shock proteins alpha-B-crystallin, MKBP, HSP25, HSP20 and cvHSP in heart and skeletal muscle. Histochem Cell Biol 122:415–425CrossRefPubMedGoogle Scholar
  14. 14.
    Golenhofen N, Ness W, Koob R, Htun P, Schaper W, Drenckhahn D (1998) Ischemia-induced phosphorylation and translocation of stress protein alpha B-crystallin to Z lines of myocardium. Am J Physiol 274:H1457–H1464PubMedGoogle Scholar
  15. 15.
    Golenhofen N, Htun P, Ness W, Koob R, Schaper W, Drenckhahn D (1999) Binding of the stress protein alphaB-crystallin to cardiac myofibrils correlates with the degree of myocardial damage during ischemia/reperfusion in vivo. J Mol Cell Cardiol 31:569–580CrossRefPubMedGoogle Scholar
  16. 16.
    Hein S, Scheffold T, Schaper J (1995) Ischemia induces early changes to cytoskeletal and contractile proteins in diseased human myocardium. J Thorac Cardiovasc Surg 110:89–98PubMedGoogle Scholar
  17. 17.
    Horwitz J (1992) Alpha-crystallin can function as a molecular chaperone. Proc Natl Acad Sci USA 89:10449–10453PubMedGoogle Scholar
  18. 18.
    Itoh-Satoh M, Hayashi T, Nishi H, Koga Y, Arimura T, Koyanagi T et al (2002) Titin mutations as the molecular basis for dilated cardiomyopathy. Biochem Biophys Res Commun 291:385–393CrossRefPubMedGoogle Scholar
  19. 19.
    Iwaki A, Nagano T, Nakagawa M, Iwaki T, Fukumaki Y (1997) Identification and characterization of the gene encoding a new member of the alpha-crystallin/small hsp family, closely linked to the alphaB-crystallin gene in a head-to-head manner. Genomics 45:386–394CrossRefPubMedGoogle Scholar
  20. 20.
    Kaplan P, Hendrikx M, Mattheussen M, Mubagwa K, Flameng W (1992) Effect of ischemia and reperfusion on sarcoplasmic reticulum calcium uptake. Circ Res 71:1123–1130PubMedGoogle Scholar
  21. 21.
    Kappe G, Franck E, Verschuure P, Boelens WC, Leunissen JA, de Jong WW (2003) The human genome encodes 10 alpha-crystallin-related small heat shock proteins: HspB1-10. Cell Stress Chaperones 8:53–61CrossRefPubMedGoogle Scholar
  22. 22.
    Keller TC (1997) Muscle structure. Molecular bungees. Nature 387:233–235Google Scholar
  23. 23.
    Klemenz R, Frohli E, Steiger RH, Schafer R, Aoyama A (1991) AlphaB-crystallin is a small heat shock protein. Proc Natl Acad Sci USA 88:3652–3656PubMedGoogle Scholar
  24. 24.
    Leijendekker WJ, Gao WD, ter Keurs HE (1990) Unstimulated force during hypoxia of rat cardiac muscle: stiffness and calcium dependence. Am J Physiol 258:H861–H869PubMedGoogle Scholar
  25. 25.
    Marban E, Kitakaze M, Koretsune Y, Yue DT, Chacko VP, Pike MM (1990) Quantification of [Ca2+]i in perfused hearts. Critical evaluation of the 5F-BAPTA and nuclear magnetic resonance method as applied to the study of ischemia and reperfusion. Circ Res 66:1255–1267Google Scholar
  26. 26.
    Morrison LE, Whittaker RJ, Klepper RE, Wawrousek EF, Glembotski CC (2004) Roles for alphaB-crystallin and HSPB2 in protecting the myocardium from ischemia–reperfusion-induced damage in a KO mouse model. Am J Physiol Heart Circ Physiol 286:H847–H855CrossRefPubMedGoogle Scholar
  27. 27.
    Neagoe C, Kulke M, del Monte F, Gwathmey JK, de Tombe PP, Hajjar RJ et al (2002) Titin isoform switch in ischemic human heart disease. Circulation 106:1333–1341CrossRefPubMedGoogle Scholar
  28. 28.
    Ray PS, Martin JL, Swanson EA, Otani H, Dillmann WH, Das DK (2001) Transgene overexpression of αBcrystallin confers simultaneous protection against cardiomyocyte apoptosis and necrosis during myocardial ischemia and reperfusion. Faseb J 15:393–402CrossRefPubMedGoogle Scholar
  29. 29.
    Redel A, Baumgartner W, Golenhofen K, Drenckhahn D, Golenhofen N (2002) Mechanical activity and force–frequency relationship of isolated mouse papillary muscle: effects of extracellular calcium concentration, temperature and contraction type. Pflugers Arch 445:297–304CrossRefPubMedGoogle Scholar
  30. 30.
    Selcen D, Engel AG (2003) Myofibrillar myopathy caused by novel dominant negative alphaB-crystallin mutations. Ann Neurol 54:804–810CrossRefPubMedGoogle Scholar
  31. 31.
    Suzuki A, Sugiyama Y, Hayashi Y, Nyu-i N, Yoshida M, Nonaka I et al (1998) MKBP, a novel member of the small heat shock protein family, binds and activates the myotonic dystrophy protein kinase. J Cell Biol 140:1113–1124CrossRefPubMedGoogle Scholar
  32. 32.
    Van Eyk JE, Powers F, Law W, Larue C, Hodges RS, Solaro RJ (1998) Breakdown and release of myofilament proteins during ischemia and ischemia/reperfusion in rat hearts: identification of degradation products and effects on the pCa–force relation. Circ Res 82:261–271PubMedGoogle Scholar
  33. 33.
    Vicart P, Caron A, Guicheney P, Li Z, Prevost MC, Faure A et al (1998) A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. Nat Genet 20:92–95CrossRefPubMedGoogle Scholar
  34. 34.
    Wang K, McClure J, Tu A (1979) Titin: major myofibrillar components of striated muscle. Proc Natl Acad Sci USA 76:3698–3702PubMedGoogle Scholar
  35. 35.
    Wu Y, Bell SP, Trombitas K, Witt CC, Labeit S, LeWinter MM et al (2002) Changes in titin isoform expression in pacing-induced cardiac failure gives rise to increased passive muscle stiffness. Circulation 106:1384–1389CrossRefPubMedGoogle Scholar
  36. 36.
    Yoshida K, Aki T, Harada K, Shama KM, Kamoda Y, Suzuki A et al (1999) Translocation of HSP27 and MKBP in ischemic heart. Cell Struct Funct 24:181–185CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • N. Golenhofen
    • 1
  • A. Redel
    • 1
  • E. F. Wawrousek
    • 2
  • D. Drenckhahn
    • 1
  1. 1.Institute of Anatomy and Cell BiologyUniversity of WürzburgGermany
  2. 2.National Eye InstituteNational Institutes of HealthBethesdaUSA

Personalised recommendations