Alterations in protein kinase C isoenzyme expression and autophosphorylation during the progression of pressure overload-induced left ventricular hypertrophy
Alterations in protein kinase C isoenzyme expression and autophosphorylation during the progression of pressure overload-induced left ventricular hypertrophy
复制标题
DOI：
10.1023/a:1021106232511
复制
发表时间：
2003-01-01
影响因子：
4.3
通讯作者：
Samarel, AM
中科院分区：
文献类型：
--
作者：
Bayer, AL;Heidkamp, MC;Samarel, AM
心肌细胞表达几种蛋白激酶C(PKC)同工酶，它们共同参与了左心室肥厚(LVH)的诱导及其向心力衰竭的过渡。个别PKC同工酶还需要转磷酸化和自磷酸化才能发挥酶的活性。为了确定PKC同工酶表达和自磷酸化在体内左心室肥厚进展过程中是否发生改变，我们对SD大鼠进行了肾上腹主动脉缩窄手术。主动脉结扎后1周、8周和24周，用抗总PKCalpha、PKCDelta和PKCepsilon及其C端自身磷酸化位点的抗体对左心室组织进行定量Western blotting。主动脉环扎术导致持续的高血压和逐渐发展的左心室肥厚，随着时间的推移发展为舒张性心力衰竭。在LVH进展的任何阶段，PKCepsilon水平和自磷酸化水平与假手术对照组没有显著差异。在诱导左心室肥厚期间，PKCalpha的表达水平也没有受到影响，但在向心力衰竭的转变过程中，PKCalpha的表达水平增加了3.2+/-0.8倍。此外，在24周结扎的动物中，PKCalpha水平与左心室肥厚程度呈高度相关。然而，自磷酸化的PKCalpha在任何时间点都没有增加。相反，PKCDelta自身磷酸化在左心室肥厚发生之前和向心力衰竭转变过程中增加。1周环带大鼠PKC Delta自身磷酸化水平升高并不伴随总PKC Delta水平的增加，而24周环扎大鼠PKC Delta水平显著升高(6.0+/-1.7倍)。此外，在24周的结扎大鼠中，磷酸化的PKC Delta水平和总的PKC Delta水平都与LVH的程度高度相关。综上所述，我们提供的间接证据表明，PKCDelta可能参与了压力超负荷LVH的诱导，而PKCDelta和PKCalpha可能都参与了向心力衰竭的过渡。
Cardiomyocytes express several isoenzymes of protein kinase C (PKC), which as a group have been implicated in the induction of left ventricular hypertrophy (LVH) and its transition to heart failure. Individual PKC isoenzymes also require transphosphorylation and autophosphorylation for enzymatic activity. To determine whether PKC isoenzyme expression and autophosphorylation are altered during LVH progression in vivo, suprarenal abdominal aortic coarctation was performed in Sprague-Dawley rats. Quantitative Western blotting was performed on LV tissue 1, 8 and 24 weeks after aortic banding, using antibodies specific for total PKCalpha, PKCdelta and PKCepsilon, and their C-terminal autophosphorylation sites. Aortic banding produced sustained hypertension and gradually developing LVH that progressed to diastolic heart failure over time. PKCepsilon levels and autophosphorylation were not significantly different from sham-operated controls during any stage of LVH progression. PKCalpha expression levels were also unaffected during the induction of LVH, but increased 3.2 +/- 0.8 fold during the transition to heart failure. In addition, there was a high degree of correlation between PKCalpha levels and the degree of LVH in 24 week banded animals. However, autophosphorylated PKCalpha was not increased at any time point. In contrast, PKCdelta autophosphorylation was increased prior to the development of LVH, and also during the transition to heart failure. The increased PKCdelta autophosphorylation in 1 week banded rats was not accompanied by an increase in total PKCdelta, whereas total PKCdelta levels were markedly increased (6.0 +/- 1.7 fold) in 24 week banded animals. Furthermore, both phosphorylated and total PKCdelta levels were highly correlated with the degree of LVH in 24 week banded rats. In summary, we provide indirect evidence to indicate that PKCdelta may be involved in the induction of pressure overload LVH, whereas both PKCdelta and PKCalpha may be involved in the transition to heart failure.