MG132, a proteasome inhibitor, attenuates pressure-overload-induced cardiac hypertrophy in rats by modulation of mitogen-activated protein kinase signals
MG132, a proteasome inhibitor, attenuates pressure-overload-induced cardiac hypertrophy in rats by modulation of mitogen-activated protein kinase signals
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MG132 是一种蛋白酶体抑制剂，通过调节丝裂原激活的蛋白激酶信号来减轻压力过载诱导的大鼠心脏肥大
DOI：
10.1093/abbs/gmq012
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发表时间：
2010-04-01
影响因子：
3.7
通讯作者：
Dong, Yugang
中科院分区：
文献类型：
--
作者：
Chen, Baolin;Ma, Yuedong;Dong, Yugang
蛋白酶体抑制物参与细胞周期调控、生长和炎症信号转导，以及有丝分裂细胞的转录调控。最近的一项研究表明，特异性蛋白酶体抑制剂MG132可能在体外抑制心肌细胞肥大。然而，其潜在的分子机制尚不清楚。本研究旨在探讨长期服用MG132对大鼠心肌肥厚的影响及其相关的分子机制。腹主动脉结扎(AAB)大鼠腹腔注射MG132(0.1 mg/kg/d)，连续8周。结果表明，MG132治疗后，AAB大鼠左室肌细胞面积、左心室重量/体重、肺/体重比值明显减小，左心室舒张期内径和室壁厚度减小，左室短轴缩短率增加。AAB可诱导心肌细胞ERK1/2、JNK1和p38的磷酸化。MG132可显著逆转AAB大鼠ERK1/2和JNK1的磷酸化水平。综上所述，我们的结果提示，长期服用MG132可减轻压力超负荷所致的AAB大鼠心肌肥厚，并通过调节ERK1/2和JNK1信号通路改善心功能。
Proteasome inhibitors are involved in cell cycle control, growth and inflammatory signaling, and transcriptional regulation of mitotic cells. A recent study has suggested that specific proteasome inhibitor MG132 may suppress cardiomyocyte hypertrophy in vitro. However, the underlying molecular mechanisms are not clear. In this study, we investigated the effects of long-term MG132 treatment on cardiac hypertrophy and the related molecular mechanisms in vivo. MG132 (0.1 mg/kg/day) was intraperitoneally injected to rats with abdominal aortic banding (AAB) for 8 weeks. Results showed that treatment with MG132 significantly attenuated left ventricular (LV) myocyte area, LV weight/body weight, and lung weight/body weight ratios, decreased LV diastolic diameter and wall thickness, and increased fractional shortening in AAB rats. AAB induced the phosphorylation of ERK1/2, JNK1, and p38 in cardiac myocytes. The elevated phosphorylation levels of ERK1/2 and JNK1 in AAB rats were significantly reversed by MG132 treatment. In conclusion, our results suggested that long-term treatment with MG132 attenuates pressure-overload-induced cardiac hypertrophy and improves cardiac function in AAB rats through regulation of ERK1/2 and JNK1 signaling pathways.