Decreased protein and phosphorylation level of the protein phosphatase inhibitor-1 in failing human hearts

Cardiovasc Res. 2004 Jan 1;61(1):87-93. doi: 10.1016/j.cardiores.2003.11.005.


Objective: The protein phosphatase inhibitor-1 (I-1) is a highly specific and potent inhibitor of type 1 phosphatases (PP1) that is active only in its protein kinase A (PKA)-phosphorylated form. I-1 ablation decreases, I-1 overexpression sensitizes beta-adrenergic signaling in the heart. It is controversial whether I-1 expression is altered in human heart failure (HF), likely because its detection in heart is difficult due to its low abundance.

Methods and results: I-1 was >500-fold enriched from left ventricular myocardium (LVM) from patients with terminal HF (n=16) and non-failing controls (NF, n=5) and quantified with an affinity-purified I-1 and a I-1 phosphospecific antiserum. In non-failing I-1 protein levels amounted to 126 fmol/mg protein. In failing hearts, I-1 protein levels were reduced by 58% and I-1 phosphorylation by 77% (P<0.001 vs. NF). I-1 phosphorylation correlated well with serine-16 phosphorylation of phospholamban (PLB) in the same hearts (P<0.001). In contrast, PLB, troponin I (TnI) and PP1 protein and TnI phosphorylation levels did not differ between HF and NF.

Conclusions: The results suggest that the reduction in I-1 protein and phosphorylation in failing human hearts leads to increased phosphatase activity which in turn may result in reduced phosphorylation of cardiac proteins such as PLB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Blotting, Western / methods
  • Calcium-Binding Proteins / analysis
  • Calcium-Binding Proteins / metabolism
  • Cardiomyopathy, Dilated / metabolism*
  • Carrier Proteins / analysis*
  • Carrier Proteins / genetics
  • Case-Control Studies
  • Endoribonucleases*
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Myocardium / chemistry*
  • Phosphoprotein Phosphatases
  • Phosphorylation
  • RNA-Binding Proteins*
  • Rabbits
  • Rats
  • Troponin I / analysis
  • Troponin I / metabolism


  • Calcium-Binding Proteins
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • RNA-Binding Proteins
  • Troponin I
  • phospholamban
  • protein phosphatase inhibitor-1
  • Endoribonucleases
  • Phosphoprotein Phosphatases
  • PPP1R8 protein, human