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Dissociation of Hsp90 interaction with eNOS impaired resistance to myocardial ischemia in BN/Mcw rat hearts
Author(s) -
An Jianzhong,
Du Jianhai,
Wei Na,
Xu Hao,
Pritchard kirkwood A,
Shi Yang
Publication year - 2009
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/fasebj.23.1_supplement.793.8
Subject(s) - enos , ischemia , medicine , chemistry , endocrinology , nitric oxide , nitric oxide synthase
Reduced bioavailability of nitric oxide ( •NO) appears to increase myocardial ischemia reperfusion injury. We previously reported that hearts from BN/Mcw rats are more resistant to global ischemia than hearts from SS/Mcw rats by a •NO dependent mechanism that was promoted by the association of hsp90 with eNOS. Recently, we developed a novel cell permeable decoy peptide TSB2 that specifically disrupts hsp90 association with eNOS. Here, we determine if TSB2 decreases resistance to myocardial ischemia in BN/Mcw rat hearts. Isolated BN/Mcw and SS/Mcw rat hearts were perfused with TSB2 (50 μg/ml) for 60 min prior to 35 min ischemia and 120 min reperfusion. Recovery of left ventricular developed pressure (RLVDP) and infarct size (IS) were measured. Immunoprecipitation and western blot analysis of heart homogenates for eNOS and hsp90 were performed. RLVDP in BN/Mcw rats (59.6±4.1%) was significantly higher than in SS/Mcw rats (32.1±4.5%). IS (%LV) in BN/Mcw rats was ~63% less than in SS/Mcw rats ((27.6±3.1% vs. 44±3.5%). TSB2 decreased RLVDP and increased IS in BN/Mcw hearts (46.4±4.7%, 36.5±4%) but not in SS/Mcw hearts (34.5±5.9%, 44.3±3.8%). Immunoblots showed that TSB2 decreased eNOS hsp90 association by 32% in BN/Mcw hearts. Taken together, TSB2 decreased resistance to myocardial ischemia by inhibiting hsp90 interactions with eNOS in isolated BN/Mcw rat hearts.