In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 277, No. 2 ( 1999-08-01), p. H474-H480
Kurzfassung:
Failing human myocardium has been associated with decreased sarcoplasmic reticulum (SR) Ca 2+ -ATPase activity. There remains controversy as to whether the regulation of SR Ca 2+ -ATPase activity is altered in heart failure or whether decreased SR Ca 2+ -ATPase activity is due to changes in SR Ca 2+ -ATPase or phospholamban expression. We therefore investigated whether alterations in cAMP-dependent phosphorylation of phospholamban may be responsible for the reduced SR Ca 2+ -ATPase activity in human heart failure. Protein levels of phospholamban and SR Ca 2+ -ATPase, detected by Western blot, were unchanged in failing compared with nonfailing human myocardium. There was decreased responsiveness to the direct activation of the SR Ca 2+ -ATPase activity by either cAMP (0.01–100 μmol/l) or protein kinase A (1–30 μg) in failing myocardium. Using the backphosphorylation technique, we observed a decrease of the cAMP-dependent phosphorylation level of phospholamban by 20 ± 2%. It is concluded that the impaired SR function in human end-stage heart failure may be due, in part, to a reduced cAMP-dependent phosphorylation of phospholamban.
Materialart:
Online-Ressource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.1999.277.2.H474
Sprache:
Englisch
Verlag:
American Physiological Society
Publikationsdatum:
1999
ZDB Id:
1477308-9
SSG:
12
