Roles of diacylglycerolkinase in cardiac hypertrophy and failure

二酰基甘油（DG）激酶（DGK）通过将DG转化为磷脂酸来终止来自DG的信号，DG是蛋白激酶C （PKC）的激活剂。因此，DGK被认为是PKC活性的衰减因子。在大鼠中，已经克隆了五种DGK同工酶，但对它们在心脏中的作用知之甚少。本研究采用原位杂交组织化学和免疫组织化学方法研究了正常状态和心肌梗死后大鼠心脏DGK同工酶的时空表达。在正常左心室（LV）心肌中，DGKα、-ε和-ζ mrna在整个心肌中均匀表达，而DGKα表达极低。心肌梗死后第3天和第7天，DGKζ在坏死区外周和边缘区表达增强，在心肌梗死后第21天，在肉芽组织中层表达增强，DGKζ在梗死区和边缘区表达增强可能与粒细胞和巨噬细胞有关。而DGKε在梗死区和交界区均低于正常左室。假手术大鼠心肌梗死后21 d存活心肌DGKε表达明显低于左室心肌，经卡托普利治疗后DGKε表达完全恢复。我们的研究结果表明，三种DGK同工酶在心脏中表达，每种同工酶在心肌梗死后的愈合和左室重塑中可能具有不同的功能特征。

Diacylglycerol (DG) kinase (DGK) terminates signaling from DG, which serves as an activator of protein kinase C (PKC), by converting DG to phosphatidic acid. DGK is thus regarded as an attertuator of the PKC activity. In rats, five DGK isozymes have been cloned but little is known about their role in the heart. In this study the spatiotemporal expression of DGK isozymes was investigated in rat hearts under a normal condition and after myocardial infarction (MI) by in situ hybrization histochemistry and immunohistochemistry. In normal left ventricular (LV) myocardium, DGKα, -ε and -ζ mRNAs were expressed evenly throughout the myocardium, although the DGKα expression was very low. In infarcted hearts, the expression of DGKζ was enhanced in the peripheral zone of the necrotic area and at the border zone 3 and 7 days after MI, and to a lesser extent in the middle layer of the granulation tissue 21 days after MI. The enhanced DGKζ expression in the infarcted and border areas could be attributed to granulocytes and macrophages. In contrast, the expression of DGKε in the infarcted and border areas was lower than that in the viable LV throughout the postoperation period. Furthermore, DGKε expression in the viable myocardium 21 days after MI decreased significantly compared with LV myocardium in the sham-operated rats, and was completely restored by treatment with captopril. Our results demonstrate that three DGK isozymes are expressed in the heart and that each isozyme might have different functional characteristics in the healing and LV remodeling after MI.