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Enhanced protein phosphorylation in hypertensive hypertrophy.
P Bokník1, I Heinroth-Hoffmann, U Kirchhefer
1Institut für Pharmakologie und Toxikologie, Universitätsklinikum Münster, Westfälische Wilhelms-Universität, Domagkstrasse 12, D-48129 Münster, Germany. boknik@uni-muenster.de
Cardiovascular Research
|September 1, 2001
Summary
In spontaneously hypertensive rats, increased Ca(2+)/calmodulin dependent protein kinase activity leads to enhanced phospholamban phosphorylation and sarcoplasmic reticulum Ca(2+) uptake, contributing to cardiac hypertrophy and failure.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Biochemistry
Background:
- Chronic pressure overload in spontaneously hypertensive rats (SHR) leads to cardiac hypertrophy and heart failure.
- Altered protein phosphorylation is implicated in the pathophysiology of cardiac hypertrophy and failure.
Purpose of the Study:
- Investigate cardiac regulatory phosphoproteins in SHR.
- Examine the kinases and phosphatases regulating protein phosphorylation in SHR.
Main Methods:
- Experiments conducted on ventricles of 12-13 week old SHR and Wistar-Kyoto rats (WKY).
- Assessed force of contraction (FOC) in isolated papillary muscles.
- Measured sarcoplasmic reticulum (SR) Ca(2+) uptake and protein expression/activity of key regulatory proteins and enzymes.
Main Results:
- SHR papillary muscles showed decreased basal and isoproterenol-stimulated FOC compared to WKY.
- Increased SR Ca(2+) uptake was observed in SHR homogenates.
- Elevated phospholamban phosphorylation at threonine-17 (PLB-PT-17) and increased Ca(2+)/calmodulin dependent protein kinase (Ca(2+)/Cam-PK) activity were found in SHR.
- Enhanced protein kinase A (PKA)-dependent phosphorylation of troponin I (TnI) was noted in SHR.
- No significant differences in protein phosphatase type 1 or 2A activity or expression were observed between SHR and WKY.
Conclusions:
- Increased Ca(2+)/Cam-PK activity in SHR enhances SR Ca(2+) uptake via increased PLB-PT-17.
- These alterations may contribute to the pathophysiological changes observed in cardiac hypertrophy in SHR.