PMID- 15786716
OWN - NLM
STAT- MEDLINE
DCOM- 20050901
LR  - 20220227
IS  - 0300-8177 (Print)
IS  - 0300-8177 (Linking)
VI  - 269
IP  - 1-2
DP  - 2005 Jan
TI  - Reduced inhibitor 1 and 2 activity is associated with increased protein 
      phosphatase type 1 activity in left ventricular myocardium of one-kidney, 
      one-clip hypertensive rats.
PG  - 49-57
AB  - In failing hearts, although protein phosphatase type 1 (PP1) activity has 
      increased, information about the regulation and status of PP1 inhibitor-1 (INH-1) 
      and inhibitor-2 (INH-2) is limited. In this study, we examined activity and 
      protein expression of PP1, INH-1 and INH-2 and phosphorylation of sarcoplasmic 
      reticulum (SR) phospholamban (PLB), a substrate of PP1 and modulator of SR 
      Ca2+-ATPase activity, in failing and non-failing hearts. These studies were 
      performed in LV myocardium of seven rats with chronic renal hypertension produced 
      by Goldblatt's one-kidney, one-clip procedure and seven age-matched sham-operated 
      normal controls (CTR). Eight weeks after surgery, LV ejection fraction, LV 
      hypertrophy, and pulmonary congestion were determined in all rats. PP1 activity 
      (nmol 32P/min/mg non-collagen protein) was assessed in LV homogenates using 
      32P-labeled phosphorylase a as substrate. INH-1 and INH-2 activity was determined 
      in the immunoprecipitate of LV homogenates and expressed as percentage inhibitory 
      activity. Using a specific antibody, LV tissue levels of PP1C and calsequestrin 
      (CSQ), a SR calcium binding protein, which is not altered in failing hearts, were 
      also determined. Further, total and phosphorylated PLB, INH-1 and INH-2 protein 
      levels were determined in the LV homogenate and phosphoprotein-enriched fraction, 
      respectively. The band density of each protein was quantified in densitometric 
      units and normalized to CSQ. RESULTS: rats with chronic renal hypertension 
      exhibited significantly reduced LV ejection fraction and increased LV hypertrophy 
      and pulmonary congestion, characteristics of chronic heart failure (CHF). We 
      found that compared to CTR, (1) both INH-1 (10.2+/-2 versus 57.5+/-1; p < 0.05) 
      and INH-2 activity (3.8+/-0.4 versus 36.2+/-4; p < 0.05) were reduced, (2) total 
      and phosphorylated PLB amount reduced, (3) protein level of phosphorylated INH-1 
      was reduced (2.32+/-0.1 versus 0.73+/-0.04; p < 0.05) whereas that of 
      phosphorylated INH-2 increased (3.05+/-0.3 versus 1.42+/-0.1; p < 0.05), and (4) 
      PP1 activity was increased approximately 2.6-fold in rats with CHF (1.59+/-0.05 
      versus 0.61+/-0.01; p < 0.05) while protein level of the catalytic subunit of PP1 
      (PP1C) increased 3.85-fold (0.77+/-0.05 versus 0.20+/-0.02; p < 0.05). These 
      results suggest that reduced inhibitory INH-1 and INH-2 activity, increased PP1C 
      protein level, and reduced PLB phosphorylation are associated with increased PP1 
      activity in failing hearts.
FAU - Gupta, Ramesh C
AU  - Gupta RC
AD  - Cardiovascular Medicine, Department of Medicine, Henry Ford Heart and Vascular 
      Institute, Henry Ford Health System, Detroit, MI 48202, USA. rgupta1@hfhs.org
FAU - Mishra, Sudhish
AU  - Mishra S
FAU - Yang, Xiao-Ping
AU  - Yang XP
FAU - Sabbah, Hani N
AU  - Sabbah HN
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (Proteins)
RN  - 0 (protein phosphatase inhibitor-1, rat)
RN  - 0 (protein phosphatase inhibitor-2)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (Protein Phosphatase 1)
SB  - IM
MH  - Animals
MH  - Cardiac Output, Low/*enzymology/etiology/metabolism
MH  - Heart Ventricles/cytology
MH  - Hypertension, Renovascular/*complications
MH  - Hypertrophy, Left Ventricular/etiology/physiopathology
MH  - Myocardium/*enzymology/metabolism
MH  - Phosphoprotein Phosphatases/*metabolism
MH  - Phosphorylation
MH  - Protein Phosphatase 1
MH  - Proteins/*metabolism
MH  - Rats
EDAT- 2005/03/25 09:00
MHDA- 2005/09/02 09:00
CRDT- 2005/03/25 09:00
PHST- 2005/03/25 09:00 [pubmed]
PHST- 2005/09/02 09:00 [medline]
PHST- 2005/03/25 09:00 [entrez]
AID - 10.1007/s11010-005-2538-x [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2005 Jan;269(1-2):49-57. doi: 10.1007/s11010-005-2538-x.