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Unmasking different mechanical and energetic roles for the small heat shock proteins CryAB and HSPB2 using genetically modified mouse hearts. FASEB J 2008 Jan;22(1):84-92

Date

09/12/2007

Pubmed ID

17846079

DOI

10.1096/fj.07-8130com

Scopus ID

2-s2.0-38049170987   34 Citations

Abstract

CryAB and HSPB2 are small heat shock proteins constitutively expressed in the heart. CryAB protects cytoskeletal organization and intermediate filament assembly; the functions of HSPB2 are unknown. The promoters of CryAB and HSPB2 share regulatory elements, making identifying their separate functions difficult. Here, using a genetic approach, we report distinct roles for these sHSPs, with CryAB protecting mechanical properties and HSPB2 protecting energy reserve. Isolated hearts of wild type mice (WT), mice lacking both sHSPs (DKO), WT mice overexpressing mouse CryAB protein (mCryAB(Tg)), and mice with no HSPB2 made by crossing DKO with mCryAB(Tg) (DKO/mCryAB(Tg)) were stressed with either ischemia/reperfusion or inotropic stimulation. Contractile performance and energetics were measured using 31P NMR spectroscopy. Ischemia/reperfusion caused severe diastolic dysfunction in DKO hearts. Recovery of [ATP] and [PCr] during reperfusion was impaired only in DKO/mCryAB(Tg). During inotropic stimulation, DKO/mCryAB(Tg) showed blunted systolic and diastolic function and revealed massive energy wasting on acute stress: |deltaG(-ATP)| decreased in DKO by 6.4 +/- 0.7 and in DKO/mCryAB(Tg) by 5.5 +/- 0.8 kJ/mol compared with only approximately 3.3 kJ/mol in WT and mCryAB(Tg). Thus, CryAB and HSPB2 proteins play nonredundant roles in the heart, CryAB in structural remodeling and HSPB2 in maintaining energetic balance.

Author List

Pinz I, Robbins J, Rajasekaran NS, Benjamin IJ, Ingwall JS

Author

Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Animals
Blotting, Western
Dobutamine
Energy Metabolism
Genetic Engineering
HSP27 Heat-Shock Proteins
Heat-Shock Proteins
Hydrolysis
Mice
Myocardial Contraction
Myocardium
Nuclear Magnetic Resonance, Biomolecular
Reperfusion Injury
alpha-Crystallin B Chain
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a