Mk. Rao et al., Glucocorticoid modulation of protein phosphorylation and sarcoplasmic reticulum function in rat myocardium, AM J P-HEAR, 281(1), 2001, pp. H325-H333
Citations number
48
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
To decipher the mechanism(s) underlying glucocorticoid action on cardiac co
ntractile function, this study investigated the effects of adrenalectomy an
d dexamethasone treatment on the contents of sarcoplasmic reticulum (SR) Ca
2+-cycling proteins, their phosphorylation by endogenous Ca2+/calmodulin-de
pendent protein kinase II (CaM kinase II), and SR Ca2+ sequestration in the
rat myocardium. Cardiac SR vesicles from adrenalectomized rats displayed s
ignificantly diminished rates of ATP-energized Ca2+ uptake in vitro compare
d with cardiac SR vesicles from control rats; in vivo administration of dex
amethasone to adrenalectomized rats prevented the decline in SR function. W
estern immunoblotting analysis showed that the relative protein amounts of
ryanodine receptor/Ca2+ release channel, Ca2+-ATPase, calsequestrin, and ph
ospholamban were neither diminished significantly by adrenalectomy nor elev
ated by dexamethasone treatment. However, the relative amount of SR-associa
ted CaM kinase II protein was increased 2.5- to 4-fold in dexamethasone-tre
ated rats compared with control and adrenalectomized rats. Endogenous CaM k
inase II activity, as judged from phosphorylation of ryanodine receptor, Ca
2+-ATPase, and phospholamban protein, was also significantly higher (50-80%
increase) in the dexamethasone-treated rats. The stimulatory effect of CaM
kinase II activation on Ca2+ uptake activity of SR was significantly depre
ssed after adrenalectomy and greatly enhanced after dexamethasone treatment
. These findings identify the SR as a major target for glucocorticoid actio
ns in the heart and implicate modification of the SR CaM kinase II system a
s a component of the mechanisms by which dexamethasone influences SR Ca2+-c
ycling and myocardial contraction.