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Dexamethasone Treatment Induces Cardiac Atrophy and Increased Proteasome Activity in MuRF1 KO mice
Author(s) -
Hwee Darren TingCheung,
Gomes Aldrin V.,
Bodine Sue C.
Publication year - 2010
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.24.1_supplement.1036.2
Subject(s) - atrophy , medicine , endocrinology , muscle atrophy , dexamethasone , proteasome , cardiac function curve , glucocorticoid , heart failure , knockout mouse , cardiac muscle , protein degradation , chemistry , receptor , biochemistry
Cardiac hypertrophy is an independent risk factor for a number of pathologies. Muscle ring finger‐1 (MuRF1) is an E3‐ubiquitin ligase that has been implicated in the regulation of cardiac mass. The objective of this study was to investigate the effect of dexamethasone (dex) treatment (3mg/kg) on cardiac mass in 6 month old female wildtype (WT) and MuRF1 knockout (KO) mice. Cardiac architecture and proteasome activity was analyzed following 28 days of dex treatment. Dex induced significant cardiac atrophy in MuRF1KO, but not WT mice. Echocardiography measurements revealed no difference in morphology or systolic function between the two groups. Dex‐treated MuRF1KO mice had significantly higher proteasome activity in the catalytic β1 and β5 subunits. Conversely, WT mice demonstrated significantly lower activity in the same catalytic subunits. These findings demonstrate that dexamethasone causes cardiac atrophy in 6 month old MuRF1 KO mice, and this atrophy may be due in part to increases in rates of protein degradation. This finding is contrary to previous reports that states that the absence of MuRF1 attenuates cardiac atrophy due to exogenous glucocorticoid treatment. This work was supported by funds from the Muscular Dystrophy Association.