PMID- 10532953
OWN - NLM
STAT- MEDLINE
DCOM- 19991116
LR  - 20190706
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 85
IP  - 9
DP  - 1999 Oct 29
TI  - Diminished basal phosphorylation level of phospholamban in the postinfarction
      remodeled rat ventricle: role of beta-adrenergic pathway, G(i) protein,
      phosphodiesterase, and phosphatases.
PG  - 848-55
AB  - Three weeks after myocardial infarction (MI) in the rat, remodeled hypertrophy of
      noninfarcted myocardium is at its maximum and the heart is in a compensated stage
      with no evidence of heart failure. Our hemodynamic measurements at this stage
      showed a slight but insignificant decrease of +dP/dt but a significantly higher
      left ventricular end-diastolic pressure. To investigate the basis of the
      diastolic dysfunction, we explored possible defects in the beta-adrenergic
      receptor-G(s/i) protein-adenylyl cyclase-cAMP-protein kinase A-phosphatase
      pathway, as well as molecular or functional alterations of sarcoplasmic reticulum
      Ca(2+)-ATPase and phospholamban (PLB). We found no significant difference in both
      mRNA and protein levels of sarcoplasmic reticulum Ca(2+)-ATPase and PLB in
      post-MI left ventricle compared with control. However, the basal levels of both
      the protein kinase A-phosphorylated site (Ser16) of PLB (p16-PLB) and the
      calcium/calmodulin-dependent protein kinase-phosphorylated site (Thr17) of PLB
      (p17-PLB) were decreased by 76% and 51% in post-MI myocytes (P<0.05),
      respectively. No change was found in the beta-adrenoceptor density, G(salpha)
      protein level, or adenylyl cyclase activity. Inhibition of phosphodiesterase and 
      G(i) protein by Ro-20-1724 and pertussis toxin, respectively, did not correct the
      decreased p16-PLB or p17-PLB levels. Stimulation of beta-adrenoceptor or adenylyl
      cyclase increased both p16-PLB and p17-PLB in post-MI myocytes to the same levels
      as in sham myocytes, suggesting that decreased p16-PLB and p17-PLB in post-MI
      myocytes is not due to a decrease in the generation of p16-PLB or p17-PLB. We
      found that type 1 phosphatase activity was increased by 32% (P<0.05) with no
      change in phosphatase 2A activity. Okadaic acid, a protein phosphatase inhibitor,
      significantly increased p16-PLB and p17-PLB levels in post-MI myocytes and
      partially corrected the prolonged relaxation of the [Ca(2+)](i) transient. In
      summary, prolonged relaxation of post-MI remodeled myocardium could be explained,
      in part, by altered basal levels of p16-PLB and p17-PLB caused by increased
      protein phosphatase 1 activity.
FAU - Huang, B
AU  - Huang B
AD  - Cardiology Division, Department of Medicine, State University of New York Health 
      Science Center and Veterans Affairs Medical Center, Brooklyn, NY 11203, USA.
FAU - Wang, S
AU  - Wang S
FAU - Qin, D
AU  - Qin D
FAU - Boutjdir, M
AU  - Boutjdir M
FAU - El-Sherif, N
AU  - El-Sherif N
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Receptors, Adrenergic, beta)
RN  - 0 (phospholamban)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (Protein Phosphatase 1)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
RN  - EC 3.1.4.- (Phosphoric Diester Hydrolases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Calcium-Binding Proteins/*metabolism
MH  - GTP-Binding Proteins/*metabolism
MH  - Heart Ventricles/*metabolism/pathology/physiopathology
MH  - Myocardial Infarction/*metabolism/pathology/physiopathology
MH  - Phosphoprotein Phosphatases/*metabolism
MH  - Phosphoric Diester Hydrolases/*metabolism
MH  - Phosphorylation
MH  - Protein Phosphatase 1
MH  - Protein Phosphatase 2
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Adrenergic, beta/*physiology
MH  - Sarcoplasmic Reticulum/metabolism
EDAT- 1999/10/26 00:00
MHDA- 1999/10/26 00:01
CRDT- 1999/10/26 00:00
PHST- 1999/10/26 00:00 [pubmed]
PHST- 1999/10/26 00:01 [medline]
PHST- 1999/10/26 00:00 [entrez]
AID - 10.1161/01.res.85.9.848 [doi]
PST - ppublish
SO  - Circ Res. 1999 Oct 29;85(9):848-55. doi: 10.1161/01.res.85.9.848.