Nankova B B, Fuchs S Y, Serova L I, Ronai Z, Wild D, Sabban E L
Department of Biochemistry and Molecular Biology, New York Medical College Valhalla, NY 10595, USA.
Stress. 1998 Dec;2(4):289-98. doi: 10.3109/10253899809167293.
Stress activated protein kinases (SAPK) are key enzymes mediating the cellular response to stressful stimuli. While they are intensively studied in cultured cells, little is known about their physiological role in vivo, or relevance to pathological conditions. Therefore we examined the effect of various times of immobilization on c-Jun N-terminal protein kinase (JNK) activity in several rat stress responsive tissues and in a number of other locations. The abundance and relative distribution of JNK isoforms, the basal levels, time course and relative magnitude of stress induced JNK activity differed among tissues and regions of the brain of the same animal. JNK immunoreactive proteins were most abundant in the brain, especially in the hippocampus, hypothalamus and frontal cortex. Marked activation in response to immobilization stress was observed in adrenal medulla, adrenal cortex, aorta and hippocampus, less pronounced in locus coeruleus. JNK was not affected in superior cervical ganglia, pituitary, hypothalamus, frontal cortex and cerebellum. In adrenal medulla, the activation of JNK by single immobilization stress is correlated with increased transcription of stress-responsive genes, tyrosine hydroxylase and dopamine beta-hydroxylase. These data suggest a potential role of JNK signal transduction pathway in mediating the long term adaptation to stressful stimuli in vivo.
应激激活蛋白激酶(SAPK)是介导细胞对应激刺激反应的关键酶。虽然它们在培养细胞中得到了深入研究,但对其在体内的生理作用或与病理状况的相关性却知之甚少。因此,我们研究了不同时长的固定对几种大鼠应激反应组织以及其他一些部位中c-Jun氨基末端蛋白激酶(JNK)活性的影响。同一动物大脑的不同组织和区域中,JNK亚型的丰度和相对分布、基础水平、应激诱导的JNK活性的时间进程和相对幅度均有所不同。JNK免疫反应性蛋白在大脑中最为丰富,尤其是在海马体、下丘脑和额叶皮质。在肾上腺髓质、肾上腺皮质、主动脉和海马体中观察到对固定应激的明显激活,在蓝斑核中则不太明显。JNK在上颈神经节、垂体、下丘脑、额叶皮质和小脑中未受影响。在肾上腺髓质中,单次固定应激对JNK的激活与应激反应基因酪氨酸羟化酶和多巴胺β-羟化酶转录的增加相关。这些数据表明JNK信号转导通路在介导体内对应激刺激的长期适应中具有潜在作用。