Laboratory of Molecular Biology and Endocrinology, Institute of Nuclear Sciences "Vinča", University of Belgrade, P.O. Box 522-090, 11001 Belgrade, Serbia.
J Neural Transm (Vienna). 2012 Nov;119(11):1275-84. doi: 10.1007/s00702-012-0776-0. Epub 2012 Feb 23.
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 (4°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.
c-Jun N 端激酶（JNKs）是重要的应激反应激酶。它们通过丝裂原活化蛋白激酶级联反应的顺序磷酸化和激活来调节细胞活动，而 JNK 激活会因各种应激源而改变。在本研究中，我们使用免疫印迹法评估 21 天社交隔离（作为慢性应激源）对循环皮质酮水平以及细胞浆和核部分 p46（磷酸化-p46/总 p46）和 p54（磷酸化-p54/总 p54）JNK 同工型的磷酸化状态的影响前额叶皮层和雄性 Wistar 大鼠海马体。此外，还检查了 JNK 核下游靶标 c-Jun（p-c-Jun/c-Jun）在 Ser63 上的磷酸化状态。两种急性应激源均导致皮质酮水平升高，导致海马体中细胞浆 p54 JNK 同工型的磷酸化状态增加，但 p46 JNK 同工型无变化，两个脑区的 c-jun 磷酸化状态无变化。慢性隔离时皮质酮水平不变，对新的急性应激源的反应性降低，导致两个脑区两个部分的 p46 和 p54 JNK 同工型的磷酸化状态不变或降低，而 c-Jun 磷酸化状态的降低仅在前额叶皮层中发现。我们的结果表明，慢性隔离后 JNK 激活受损可能导致 JNK 信号中断，这可能与抑郁或持久的神经元重塑等神经精神疾病有关。
