期刊
FASEB JOURNAL
卷 22, 期 1, 页码 84-92出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.07-8130com
关键词
transgenesis; cardiac function
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P50HL052320, R01HL063834, R01HL063985] Funding Source: NIH RePORTER
- NHLBI NIH HHS [R01-HL63834, R01-HL63985, HL52320] Funding Source: Medline
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 mCryABTg (DKO/ mCryAB(Tg)) were stressed with either ischemia/reperfusion or inotropic stimulation. Contractile performance and energetics were measured using P-31 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/ mCryABTg showed blunted systolic and diastolic function and revealed massive energy wasting on acute stress: vertical bar Delta G(similar to ATP)vertical bar similar to decreased in DKO by 6.4 +/- 0.7 and in DKO/mCryAB(Tg) by 5.5 +/- 0.8 kJ/mol compared with only similar to 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.
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