Testa Marco, Rocca Bianca, Spath Lucia, Ranelletti Franco O, Petrucci Giovanna, Ciabattoni Giovanni, Naro Fabio, Schiaffino Stefano, Volpe Massimo, Reggiani Carlo
Department of Cardiology, Azienda Ospedaliera Sant'Andrea, Via di Grottarossa 1035, 00189 Roma, Italy.
J Appl Physiol (1985). 2007 Oct;103(4):1412-8. doi: 10.1152/japplphysiol.00288.2007. Epub 2007 Aug 2.
Conflicting data have been reported on cyclooxygenase (COX)-1 and COX-2 expression and activity in striated muscles, including skeletal muscles and myocardium, in particular it is still unclear whether muscle cells are able to produce prostaglandins (PGs). We characterized the expression and enzymatic activity of COX-1 and COX-2 in the skeletal muscles and in the myocardium of mice, rats and humans. By RT-PCR, COX-1 and COX-2 mRNAs were observed in homogenates of mouse and rat hearts, and in different types of skeletal muscles from all different species. By Western blotting, COX-1 and -2 proteins were detected in skeletal muscles and hearts from rodents, as well as in skeletal muscles from humans. Immunoperoxidase stains showed that COX-1 and -2 were diffusely expressed in the myocytes of different muscles and in the myocardiocytes from all different species. In the presence of arachidonic acid, which is the COX enzymatic substrate, isolated skeletal muscle and heart samples from rodents released predominantly PGE(2). The biosynthesis of PGE(2) was reduced between 50 and 80% (P < 0.05 vs. vehicle) in the presence of either COX-1- or COX-2-selective blockers, demonstrating that both isoforms are enzymatically active. Exogenous PGE(2) added to isolated skeletal muscle preparations from rodents did not affect contraction, whereas it significantly fastened relaxation of a slow type muscle, such as soleus. In conclusion, COX-1 and COX-2 are expressed and enzymatically active in myocytes of skeletal muscles and hearts of rodents and humans. PGE(2) appears to be the main product of COX activity in striated muscles.
关于环氧化酶（COX）-1和COX-2在横纹肌（包括骨骼肌和心肌）中的表达及活性，已有相互矛盾的数据报道，尤其是肌肉细胞是否能够产生前列腺素（PGs）仍不清楚。我们对小鼠、大鼠和人类骨骼肌及心肌中COX-1和COX-2的表达及酶活性进行了表征。通过逆转录聚合酶链反应（RT-PCR），在小鼠和大鼠心脏匀浆以及所有不同物种的不同类型骨骼肌中均观察到COX-1和COX-2信使核糖核酸（mRNAs）。通过蛋白质免疫印迹法，在啮齿动物的骨骼肌和心脏以及人类骨骼肌中检测到COX-1和 -2蛋白。免疫过氧化物酶染色显示，COX-1和 -2在所有不同物种不同肌肉的肌细胞和心肌细胞中均呈弥漫性表达。在存在COX酶底物花生四烯酸的情况下，从啮齿动物分离的骨骼肌和心脏样本主要释放前列腺素E2（PGE2）。在存在COX-1或COX-2选择性阻滞剂的情况下，PGE2的生物合成减少了50%至80%（与溶剂相比，P < 0.05），表明这两种同工型均具有酶活性。添加到从啮齿动物分离的骨骼肌制剂中的外源性PGE2不影响收缩，而它显著加快了慢肌类型（如比目鱼肌）的舒张。总之，COX-1和COX-2在啮齿动物和人类骨骼肌及心脏的肌细胞中表达且具有酶活性。PGE2似乎是横纹肌中COX活性的主要产物。
