Zhao Y, Xu D, Quaegebeur J M, Emala C W, Sun L S
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Pediatr Cardiol. 2002 Sep-Oct;23(5):536-41. doi: 10.1007/s00246-001-0097-9.
We have previously demonstrated that both basal and isoproterenol-stimulated activities of myocardial adenylyl cyclase were greater in cyanotic patients with tetralogy of Fallet (TOF) than those in acyanotic patients. However, it was not determined whether increased enzyme activity was related to a similar increase in adenylyl cyclase protein and mRNA expression. In the current study, we examined the mRNA and protein expression of cardiac adenylyl cyclase, types V and VI, in cyanotic and acyanotic patients with TOF. Ribonuclease protection assays and immunoblotting were performed on myocardial specimens obtained from cyanotic patients with TOF and acyanotic patients with TOF or ventricular septal defect. We demonstrated that in both cyanotic and acyanotic patients, there was more type V adenylyl cyclase mRNA than type VI. Types V and VI cardiac adenylyl cyclase mRNA were significantly increased in myocardium of the cyanotic group compared to the acyanotic group. Protein expression of both V and VI adenylyl cyclases was correspondingly upregulated in cyanotic patients compared to acyanotic patients. Our results indicate that gene and protein expression of cardiac adenylyl cyclases, types V and VI, is increased in the cyanotic myocardium. These results suggest that chronic hypoxemia may regulate the expression of adenylyl cyclase enzymes.
我们先前已经证明，法洛四联症（TOF）的青紫型患者心肌腺苷酸环化酶的基础活性和异丙肾上腺素刺激的活性均高于无青紫型患者。然而，尚未确定酶活性增加是否与腺苷酸环化酶蛋白和mRNA表达的类似增加有关。在当前研究中，我们检测了TOF青紫型和无青紫型患者心脏V型和VI型腺苷酸环化酶的mRNA和蛋白表达。对取自TOF青紫型患者以及TOF或室间隔缺损无青紫型患者的心肌标本进行了核糖核酸酶保护分析和免疫印迹。我们证明，在青紫型和无青紫型患者中，V型腺苷酸环化酶mRNA均多于VI型。与无青紫型组相比，青紫型组心肌中V型和VI型心脏腺苷酸环化酶mRNA显著增加。与无青紫型患者相比，青紫型患者中V型和VI型腺苷酸环化酶的蛋白表达相应上调。我们的结果表明，青紫型心肌中V型和VI型心脏腺苷酸环化酶的基因和蛋白表达增加。这些结果提示，慢性低氧血症可能调节腺苷酸环化酶的表达。
