Chronic isolation stress compromises JNK/c-Jun signaling in rat brain
Chronic isolation stress compromises JNK/c-Jun signaling in rat brain
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DOI：
10.1007/s00702-012-0776-0
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发表时间：
2012-11-01
影响因子：
3.3
通讯作者：
Demajo, Miroslav
中科院分区：
文献类型：
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作者：
Filipovic, Dragana;Zlatkovic, Jelena;Demajo, Miroslav
c-Jun氨基末端激酶（JNK）是重要的应激反应激酶。它们通过有丝分裂原活化蛋白激酶级联反应通过连续的磷酸化和活化来调节细胞活性，而JNKs活化在响应各种应激物时改变。在本研究中，我们使用免疫印迹来评估21天的社会隔离作为慢性应激源的影响，单独或与2小时急性制动或冷结合（4A ℃）对循环皮质酮水平和p46磷酸化状态的应激（磷酸化p46/总p46）和p54（磷酸化p54/总p54）JNK亚型在雄性Wistar大鼠前额叶皮层和海马的胞质和核部分中的表达。此外，检查JNK核下游靶c-Jun（p-c-Jun/c-Jun）在Ser 63上的磷酸化状态。两种急性应激源与CORT水平升高导致增加的磷酸化状态的胞质p54 JNK亚型，但不是p46 JNK亚型只在海马和c-jun的磷酸化状态没有变化，在两个大脑区域。慢性隔离与不变的CORT水平和减少对新的急性应激源的反应，导致不变或减少磷酸化状态的p46和p54 JNK亚型在两个馏分和两个大脑区域，而减少c-Jun磷酸化状态只发现在前额皮质。我们的研究结果表明，慢性隔离后受损的JNK激活可能导致JNK信号传导中断，这可能与神经精神疾病，如抑郁症或长期神经元重塑有关。
The c-Jun NH2-terminal kinases (JNKs) are important stress-responsive kinases. They regulate cellular activities by sequential phosphorylation and activation through a mitogen-activated protein kinase cascade, whereas JNKs activation is altered in response to various stressors. In the present study, we used immunoblotting to assess the effect of 21 day of social isolation as the chronic stressor, either sole and in combination with 2 h of acute immobilization or cold (4A degrees C) stress on circulating corticosterone level and phosphorylation status of p46 (phospho-p46/total p46) and p54 (phospho-p54/total p54) JNK isoforms in the cytosolic and nuclear fraction of the prefrontal cortex and hippocampus of male Wistar rats. Also, the phosphorylation status of JNK nuclear down-stream target c-Jun (p-c-Jun/c-Jun) on Ser63 was examined. Both acute stressors with elevated CORT levels led to increased phosphorylation status of cytosolic p54 JNK isoforms but not p46 JNK isoforms only in the hippocampus and no change in phosphorylation status of c-jun in both brain regions. Chronic isolation with unaltered CORT level and reduced responsiveness to novel acute stressors, led to unchanged or reduced phosphorylation status of p46 and p54 JNK isoforms in both fractions and both brain regions, whereas the decrease of c-Jun phosphorylation status was found only in the prefrontal cortex. Our results suggest that compromised JNKs activation following chronic isolation may lead to interruption of JNK signaling, which could be related with neuropsychiatric disorders such as depression or long-lasting neuronal remodeling.