Braun Martin U, LaRosée Paul, Schön Steffen, Borst Mathias M, Strasser Ruth H
Department of Cardiology, Medical Clinic II, University of Technology Dresden, Fetscherstr. 76, Dresden, Germany.
Cardiovasc Res. 2002 Oct;56(1):52-63. doi: 10.1016/s0008-6363(02)00511-4.
Protein kinase C (PKC) plays a key role in myocardial hypertrophy. To evaluate whether its isoforms are expressed differentially during gradual development of pressure-overload-induced cardiac hypertrophy, banding of the ascending aorta was used as an experimental model of left ventricular hypertrophy.
One, 7 and 30 days after sham operation or aortic banding in male Wistar rats, the PKC activity and the expression of the cardiac PKC isozymes (PKC-alpha, -delta, - epsilon and -zeta), both at the protein and the mRNA level, were determined in the left and right ventricle.
Left ventricular hypertrophy developed rapidly as early as 1 day after aortic banding followed by further progression at day 7 and day 30. This was paralleled by an increased total PKC enzyme activity in the cytosol fraction and a selectively enhanced protein expression of PKC-delta (day 7, 267+/-18%; day 30, 289+/-12%) and PKC-alpha (day 7, 212+/-20%; day 30, 193+/-14%). The protein amount of PKC- epsilon was not changed in either group. This differential protein expression was associated with a significant increase of the absolute mRNA levels for PKC-delta and PKC-alpha up to 202+/-20% (day 30) and 177+/-17% (day 30), whereas significant alterations in the PKC- epsilon mRNA levels were not detected. A selective upregulation of PKC-alpha and PKC-delta, both on the protein and on the mRNA level, was also noted in the right ventricle during the development of right ventricular hypertrophy, suggesting an adaptive response following elevated left ventricular enddiastolic pressure after long-term aortic banding for 30 days.
This study characterizes in the right and left ventricle a differential regulation of the dominant PKC isozymes in pressure-overload cardiac hypertrophy both at the protein and the mRNA level.
蛋白激酶C（PKC）在心肌肥大中起关键作用。为评估其同工型在压力超负荷诱导的心脏肥大逐渐发展过程中是否存在差异表达，采用升主动脉缩窄作为左心室肥大的实验模型。
在雄性Wistar大鼠进行假手术或主动脉缩窄后1天、7天和30天，测定左、右心室中PKC活性以及心脏PKC同工型（PKC-α、-δ、-ε和-ζ）在蛋白质和mRNA水平的表达。
主动脉缩窄后1天，左心室肥大迅速发展，随后在第7天和第30天进一步进展。这与胞质部分总PKC酶活性增加以及PKC-δ（第7天，267±18%；第30天，289±12%）和PKC-α（第7天，212±20%；第30天，193±14%）的蛋白表达选择性增强平行。两组中PKC-ε的蛋白量均未改变。这种差异蛋白表达与PKC-δ和PKC-α的绝对mRNA水平显著增加相关，分别高达202±20%（第30天）和177±17%（第30天），而未检测到PKC-ε mRNA水平的显著变化。在右心室肥大发展过程中，在蛋白质和mRNA水平上也观察到PKC-α和PKC-δ的选择性上调，提示长期主动脉缩窄30天后左心室舒张末期压力升高后的适应性反应。
本研究在左、右心室中均表明，在压力超负荷心脏肥大中，主要PKC同工型在蛋白质和mRNA水平上存在差异调节。
