Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mild pulmonic stenosis was performed in dogs to evaluate the effect of systolic pressures overloading on the activity and subunits of myosin in the early hypertrophied right ventricle. Three weeks following pulmonary constriction, six hypertrophied dogs were sacrificed and compared to six sham-operated dogs which served as controls. In the right ventricular free wall of hypertrophied right ventricles (HRV), the heart/body weight was 46% greater than that of normal right ventricles (NRV) (p less than 0.01). Myosin ATPase activity (Vmax values) in mumoles phosphate/mg/min, was elevated significantly in the stressed ventricle for both K+ and Ca++ activity in hypertrophied right ventricles. Associated with the increase in myosin activity, there was an increase in proportion of heavy to light chains in myosin from HRV. There were approximately 2 moles of myosin light chains per mole of myosin heavy chains in NRV and approximately 1 mole of myosin light chains per mole of myosin heavy chains in HRV. The proportion of light chain C1 to C2, did not change in myosin from NRV and HRV. Of the C1 light chains, according to two-dimensional gel electrophoresis, there was less C1d as compared to C1c in HRV as compared to NRV. Thus K+- and Ca++- activated myosin is elevated in early canine HRV by pressure overload. It is suggested taht the augmented myosin activity is due to a reduction of light chain inhibition of myosin ATPase activity, which appears to result from the slower turnover rate of myosin light chains relative to heavy chains. Furthermore, when myosin light chains are added to hypertrophied right ventricular myosin, the ATPase activity is lowered.
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PMID:Modulation of myosin in right ventricular hypertrophy. 12 38

Mild pulmonic stenosis, induced in dogs by banding the pulmonary artery, elevated right ventricular peak systolic pressure to 60% above the control and elevated right ventricular K+- and Ca2+- activated myosin ATPase activities. In contrast, severe pulmonic stenosis, which elevated right ventricular peak systolic pressure to 300% above the control, did not produce an increase in myosin enzymatic ATPase Vmax values but caused a decrease in myosin activity. Mild aortic stenosis, induced by banding the ascending aorta, forcing a transaortic pressure gradient of 25 mm Hg, caused an elevation in left ventricular muosin ATPase, whereas severe aortic banding, brought about by creating a transaortic pressure gradient of 55 mm Hg, never caused an elevation in left ventricular myosin enzymatic Vmax values, but, like severe pulmonic banding, caused a decrease in K+- and Ca2+- activated myosin activities. Normal left ventricular myosin Vmax values in mumol of PO4/mg-min at 37 degrees C were: K+ = 2.84 +/- 0.22, and Ca2+ = 0.97 +/- 0.14. For right ventricular myosin they were: K+ = 2.15 +/- 0.16, and Ca2+ =0.74 +/- 0.10. Analyses of tissue gases, based on mass spectrometry data, showed that the hypertrophied ventricles had an elevated tissue pCO2 and an elevation in the cGMP/cAMP ratio.
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PMID:Differential responses of canine myosin ATPase activity and tissue gases in the pressure-overloaded ventricle dependent upon degree of obstruction: mild versus severe pulmonic and aortic stenosis. 20 99

Mild pulmonic stenosis in the dog, where right ventricular peak systolic pressure was increased approximately 150% at the time of sacrifice, induced 100% or more increase in right ventricular free wall weight by 3 weeks postoperative. Accompanying cardiac hypertrophy at these postoperative times, there was a decrease in both tissue PO2 levels and cAMP concentrations in the hemodynamically stressed ventricle, the right ventricle. Myosin ATPase activity was elevated as well as the velocity of contractile element shortening. The hemodynamically nonstressed left ventricle did not hypertrophy at these early postoperative times.
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PMID:Changes in cAMP concentrations during chronic cardiac hypertrophy. 21 47

Noonan syndrome with multiple lentigines (NSML) is primarily caused by mutations in the nonreceptor protein tyrosine phosphatase SHP2 and associated with congenital heart disease in the form of pulmonary valve stenosis and hypertrophic cardiomyopathy (HCM). Our goal was to elucidate the cellular mechanisms underlying the development of HCM caused by the Q510E mutation in SHP2. NSML patients carrying this mutation suffer from a particularly severe form of HCM. Drawing parallels to other, more common forms of HCM, we hypothesized that altered Ca(2+) homeostasis and/or sarcomeric mechanical properties play key roles in the pathomechanism. We used transgenic mice with cardiomyocyte-specific expression of Q510E-SHP2 starting before birth. Mice develop neonatal onset HCM with increased ejection fraction and fractional shortening at 4-6 wk of age. To assess Ca(2+) handling, isolated cardiomyocytes were loaded with fluo-4. Q510E-SHP2 expression increased Ca(2+) transient amplitudes during excitation-contraction coupling and increased sarcoplasmic reticulum Ca(2+) content concurrent with increased expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase. In skinned cardiomyocyte preparations from Q510E-SHP2 mice, force-velocity relationships and power-load curves were shifted upward. The peak power-generating capacity was increased approximately twofold. Transmission electron microscopy revealed that the relative intracellular area occupied by sarcomeres was increased in Q510E-SHP2 cardiomyocytes. Triton X-100-based myofiber purification showed that Q510E-SHP2 increased the amount of sarcomeric proteins assembled into myofibers. In summary, Q510E-SHP2 expression leads to enhanced contractile performance early in disease progression by augmenting intracellular Ca(2+) cycling and increasing the number of power-generating sarcomeres. This gives important new insights into the cellular pathomechanisms of Q510E-SHP2-associated HCM.
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PMID:Elevated Ca2+ transients and increased myofibrillar power generation cause cardiac hypercontractility in a model of Noonan syndrome with multiple lentigines. 2572 91