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Unmasking different mechanical and energetic roles for the small heat shock proteins CryAB and HSPB2 using genetically modified mouse hearts
Author(s) -
Pinz Ilka,
Robbins Jeffrey,
Rajasekaran Namakkal S.,
Benjamin Ivor J.,
Ingwall Joanne S.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-8130com
Subject(s) - heat shock protein , inotrope , stimulation , medicine , shock (circulatory) , genetically modified mouse , energy metabolism , cardiology , transgene , biophysics , chemistry , biology , biochemistry , gene
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/ m CryAB Tg ) were stressed with either ischemia/reper‐fusion or inotropic stimulation. Contractile performance and energetics were measured using 31 PNMR spectroscopy. Ischemia/reperfusion caused severe dia‐stolic 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: |∆G ‐ATP | decreased in DKO by 6.4 ± 0.7 and in DKO/mCryAB Tg by 5.5 ± 0.8 kJ/mol compared with only ~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.— Pinz, I., Robbins, J., Rajasekaran, N. S., Benjamin, I. J., Ingwall, J. S. Unmasking different mechanical and energetic roles for the small heat shock proteins CryAB and HSPB2 using genetically modified mouse hearts. FASEB J. 22, 84–92 (2008)