Chronic stress and excessive glucocorticoid exposure both lead to altered Neuregulin-1/ErbB signaling in rat myocardium
Chronic stress and excessive glucocorticoid exposure both lead to altered Neuregulin-1/ErbB signaling in rat myocardium
复制标题
慢性应激和过量糖皮质激素暴露都会导致大鼠心肌中 Neuregulin-1/ErbB 信号传导发生改变
DOI：
10.1016/j.steroids.2016.04.011
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发表时间：
2016-08-01
期刊：
影响因子：
2.7
通讯作者：
Jiang, Pei
中科院分区：
文献类型：
--
作者：
Dang, Ruili;Guo, Yujin;Jiang, Pei
暴露于慢性压力或过量的糖皮质激素与抑郁症和心脏病的发展有关，但潜在的机制仍然不明确。虽然最近的证据表明，神经调节蛋白-1（NRG 1）及其ErbB受体在心脏功能中起着重要作用，但NRG 1/ErbB通路与应激诱导的抑郁症和心功能不全的并发症之间的生物学联系仍然是未知的。因此，我们研究了NRG 1和ErbB受体的蛋白表达在大鼠心肌慢性不可预测的轻度应激（CIMIS）或大鼠治疗两种不同剂量（0.2和2毫克/公斤/天，分别）的地塞米松（Dex）。应激大鼠心肌NRG 1和磷酸化ErbB 4（pErbB 4）表达升高，而ErbB 2和pErbB 2表达受到抑制。较低剂量的Dex增强了心肌NRG 1/ ErbB信号传导，但随着剂量的增加，ErbB 4保持激活，ErbB 2和pErbB 2的表达受到损害。Dex和2 mg/kg Dex均抑制下游Akt和ERK磷酸化。虽然低剂量Dex增加心肌抗凋亡Bcl-xl表达，但在高剂量Dex处理的大鼠中发现Bcl-xl表达显著降低。同时，两种浓度的地塞米松和地塞米松均能诱导凋亡相关蛋白Bax的表达。本研究首次揭示了NRG 1/ErbB系统在应激心脏中的适应性反应，提示NRG 1/ErbB通路可能参与了应激性心功能不全的发生。(C)2016 Elsevier Inc. All rights reserved.
Exposure to chronic stress or excess glucocorticoids is associated with the development of depression and heart disease, but the underlying mechanisms remain equivocal. While recent evidence has indicated that Neuregulin-1 (NRG1) and its ErbB receptors play an essential role in cardiac function, much is still unknown concerning the biological link between NRG1/ErbB pathway and the stress-induced comorbidity of depression and cardiac dysfunction. Therefore, we examined the protein expression of NRG1 and ErbB receptors in the myocardium of rats following chronic unpredictable mild stress (CUMS) or rats treated with two different doses (0.2 and 2 mg/kg/day, respectively) of dexamethasone (Dex). The stressed rats showed elevated expression of NRG1 and phosphorylated ErbB4 (pErbB4) in the myocardium, whereas ErbB2 and pErbB2 were inhibited. The lower dose of Dex enhanced myocardial NRG1 / ErbB signaling, but as the dose is increased, while ErbB4 remained activated, the expression of ErbB2 and pErbB2 became compromised. Both CUMS and 2 mg/kg of Dex suppressed the downstream Akt and ERK phosphorylation. Although the lower dose of Dex increased myocardial antiapoptotic Bcl-xl expression, a significant decrease of Bcl-xl expression was found in rats treated with the higher dose. Meanwhile, both CUMS and two different doses of Dex induced proapoptotic Bax level. Combined, our data firstly showed (mal)adaptive responses of NRG1/ErbB system in the stressed heart, indicating the potential involvement of NRG1/ErbB pathway in the stress-induced cardiac dysfunction. (C) 2016 Elsevier Inc. All rights reserved.