Sarcoplasmic reticulum gene expression in pressure overload-induced cardiac hypertrophy in rabbit.
Pressure overload (PO)-induced cardiac hypertrophy in rabbits has been utilized extensively to study alterations in systolic and diastolic functions of the heart. In earlier studies we showed that the levels of mRNA encoding two important sarcoplasmic reticulum (SR) proteins, the cardiac/slow-twitch muscle Ca(2+)-ATPase (SERCA2a) and phospholamban, were decreased in PO rabbit hearts. In this study, we analyzed the expression of the Ca(2+)-release channel (ryanodine receptor), calsequestrin, SERCA2a, and phospholamban in PO-induced cardiac hypertrophy after 2, 4, 8, and 16 days of pulmonary artery banding. Northern blot and slot blot analyses showed that the steady-state level of mRNA encoding the cardiac ryanodine receptor, SERCA2a, and phospholamban was decreased significantly as early as 2 days after PO. In 16-day PO hearts, SERCA2a mRNA was reduced to 7.9 +/- 3.4% (P < 0.05), phospholamban mRNA was reduced to 15.9 +/- 6.5% (P < 0.05), and ryanodine receptor mRNA was reduced to 49.2 +/- 23.6% (P < 0.05). In this study, calsequestrin mRNA levels were also reduced to 29.9 +/- 15.2% by day 16 (P < 0.05). ATP-dependent Ca2+ uptake was reduced to 78% (P < 0.05); in contrast, the steady-state formation of ATPase phosphoenzyme was reduced to 81% of control (P < 0.05) and Ca(2+)-ATPase protein was reduced to 78% of control (P < 0.05) in crude SR vesicles or total muscle homogenate obtained from 16-day PO hearts. On the basis of these data, we propose that decreases in the expression of SR proteins may contribute to dysfunctions seen in systolic and diastolic properties of the hypertrophied myocardium.
Matsui
H
H
Department of Molecular Physiology and Biophysics, University of Vermont College of Medicine, Burlington 05405.
MacLennan
D H
DH
Alpert
N R
NR
Periasamy
M
M
D000199:Actins / Q000235:genetics; D000818:Animals; D015220:Calcium Channels / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D002155:Calsequestrin / Q000235:genetics; D006332:Cardiomegaly / Q000209:etiology* / Q000235:genetics*; D015870:Gene Expression; D006973:Hypertension / Q000150:complications*; D008297:Male; D009124:Muscle Proteins / Q000235:genetics; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D000099211:Phospholamban
D000199:Actins; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D002155:Calsequestrin; D009124:Muscle Proteins; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D000099211:Phospholamban