Reciprocall modulation of mitogen-activated protein kinases and mitogen-activated protein kinase phosphatase 1 and 2 in failing human myocardium
Reciprocall modulation of mitogen-activated protein kinases and mitogen-activated protein kinase phosphatase 1 and 2 in failing human myocardium
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DOI：
10.1054/jcaf.2002.32755
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发表时间：
2002-04-01
影响因子：
6
通讯作者：
Singh, K
中科院分区：
文献类型：
--
作者：
Communal, C;Colucci, WS;Singh, K
背景：丝裂原激活蛋白激酶 (MAPK)，由 ERK1/2 组成。 JNK 和 p38 激酶家族在体外调节心肌细胞生长和凋亡中发挥关键作用。 MAPK 的活性受双特异性 MAPK 磷酸酶 (MKP) 的调节。由于心肌衰竭与心肌细胞肥大和细胞凋亡相关，MAPKs可能在人类心肌衰竭中发挥病理生理作用。 方法和结果：我们测量了特发性扩张型心肌病引起的终末期衰竭患者移植时移植的心肌中MAPKs活性以及MAPKs和MKPs（MKP-1和MKP-2）的蛋白水平。 （n = 5-7）。使用未衰竭的供体心脏（n = 5-7）进行比较。尽管衰竭心脏中 JNK1/2 和 p38 激酶的蛋白质水平与正常心脏中的水平没有差异，但两者的活性均下降 (P < .05)。尽管衰竭心脏中 ERK1/2 的蛋白质水平增加了 3 倍以上，但 ERK1/2 活性并未增加。衰竭心脏中 MKP-2 的表达显着增加，而 7 个衰竭心脏中的 5 个中 MKP-1 表达增加，正如 Western 分析所珍视的那样。结论：在衰竭的人类心肌中，JNK1/2 和 p38 活性降低。因此，MKP 表达增加可能导致人类衰竭心肌中 MAPK 活性降低。
Background: Mitogen-activated protein kinases (MAPKs), consisting of the ERK1/2. JNKs, and p38-kinase families, play a key role in the regulation of myocyte growth and apoptosis in vitro. The activity of MAPKs is regulated by dual-specificity MAPK phosphatases (MKPs). Because myocardial failure is associated with myocyte hypertrophy and apoptosis, MAPKs may play a pathophysiologic role in human myocardial failure.Methods and Results: We measured MAPKs activities and the protein levels of MAPKs and MKPs (MKP-1 and MKP-2) in the myocardium explanted at the time of transplantation from patients with end-stage failure caused by idiopathic dilated cardiomyopathy (n = 5-7). Nonfailing donor hearts (n = 5-7) were used for comparison. Although the protein levels for JNK1/2 and p38-kinase in failing hearts were not different from levels in nonfailing hearts, the activities of both were decreased (P < .05). Despite a > 3-fold increase in the protein level for ERK1/2 in failing hearts, ERK1/2 activity was not increased. Expression of MKP-2 was significantly increased in failing hearts, while expression of MKP-1 was increased in 5 of 7 failing hearts as treasured by Western analysis.Conclusions: JNK1/2 and p38 activities are decreased in failing human myocardium. Increased expression of MKPs may therefore contribute to decreased MAPKs activity in failing human myocardium.