Decreased protein and phosphorylation level of the protein phosphatase inhibitor-1 in failing human hearts
Decreased protein and phosphorylation level of the protein phosphatase inhibitor-1 in failing human hearts
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DOI：
10.1016/j.cardiores.2003.11.005
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发表时间：
2004-01-01
影响因子：
10.8
通讯作者：
Eschenhagen, T
中科院分区：
文献类型：
--
作者：
El-Armouche, A;Pamminger, T;Eschenhagen, T
目的：蛋白磷酸酶抑制剂-1 （I-1）是一种高度特异性和有效的1型磷酸酶（PP1）抑制剂，仅在其蛋白激酶a （PKA）磷酸化形式中具有活性。I-1消融减少，I-1过表达使心脏β -肾上腺素能信号敏感。I-1在人心力衰竭（HF）中表达是否改变尚存争议，可能是因为其丰度低，在心脏中难以检测。方法和结果：终末期HF患者（n = 16）和非衰竭对照组（NF, n = 5）左心室心肌（LVM）中I-1的富集量为>500倍，并用亲和纯化的I-1和I-1磷特异性抗血清进行定量。在正常情况下，I-1蛋白水平为126 fmol/mg蛋白。在衰竭心脏中，I-1蛋白水平降低58%，I-1磷酸化降低77% （P < 0.001 vs. NF）。在相同的心脏中，I-1磷酸化与PLB丝氨酸-16磷酸化具有良好的相关性（P < 0.001）。相比之下，HF和NF之间PLB、肌钙蛋白I （TnI）、PP1蛋白和TnI磷酸化水平没有差异。结论：研究结果表明，人类衰竭心脏I-1蛋白和磷酸化的减少导致磷酸酶活性的增加，进而可能导致心脏蛋白（如PLB）磷酸化的减少。(C) 2003年欧洲心脏病学会。Elsevier B.V.版权所有。
Objective: The protein phosphatase inhibitor-1 (I-1) is a highly specific and potent inhibitor of type 1 phosphatases (PP1) that is active only in its protein kinase A (PKA)-phosphorylated form. I-1 ablation decreases, I-1 overexpression sensitizes beta-adrenergic signaling in the heart. It is controversial whether I-1 expression is altered in human heart failure (HF), likely because its detection in heart is difficult due to its low abundance. Methods and results: I-1 was >500-fold enriched from left ventricular myocardium (LVM) from patients with terminal HF (n = 16) and non-failing controls (NF, n = 5) and quantified with an affinity-purified I-1 and a I-1 phosphospecific antiserum. In non-failing I-1 protein levels amounted to 126 fmol/mg protein. In failing hearts, I-1 protein levels were reduced by 58% and I-1 phosphorylation by 77% (P < 0.001 vs. NF). I-1 phosphorylation correlated well with serine-16 phosphorylation of phospholamban (PLB) in the same hearts (P < 0.001). In contrast, PLB, troponin I (TnI) and PP1 protein and TnI phosphorylation levels did not differ between HF and NF. Conclusions: The results suggest that the reduction in I-1 protein and phosphorylation in failing human hearts leads to increased phosphatase activity which in turn may result in reduced phosphorylation of cardiac proteins such as PLB. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.