Lee J K, Hwang W S, Lee Y D, Han P L
Department of Anatomy, Inha University Medical School, Inchon, 402-751, South Korea.
Brain Res Mol Brain Res. 1999 Mar 20;66(1-2):133-40. doi: 10.1016/s0169-328x(99)00035-2.
Stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), a member of the MAP kinase (MAPK) superfamily, plays a key role in a variety of cellular processes. It is well established that SAPK/JNK activation is controlled by SEK1/MKK4, an up-stream MAP kinase kinase. To gain insight into the role of SEK1 during embryonic development and in adult life, we examined the temporal and spatial patterns of sek1 expression in mice by using in situ hybridization and immunohistochemical study. Dynamic changes of sek1 expression were observed during embryogenesis. Strong sek1 expression was detected in most of the central nervous system and in liver and thymus during early stages of development. While the sek1 expression in nervous system increases over time, expression in fetal liver and thymus gradually decreases as embryogenesis proceeds. High level of the sek1 expression in the central nervous system was persisted throughout postnatal development and remained at a stable level in adult brain. These observations provide an anatomical basis for the vital role(s) of SEK1 in development, for example, in hepatogenesis and/or neurogenesis. Although SEK1 was widely expressed in adult brain, more strong expression of the sek1 was observed at layers 2 and 6 in cerebral cortex, in Purkinje cells of cerebellum, and also in hypothalamic nuclei. The strongest expression of the sek1 was found in the CA3 region of hippocampus, the region being highly vulnerable to exitotoxicity-induced apoptosis in kainate-treated animal models. Interestingly, SEK1 was localized not only in cytoplasm but in dendrites and/or in nucleus of neurons depending on the regions of adult mouse brain. Taken together, these results suggest multiple roles of the SEK1 during embryogenesis and in adult brain.
应激激活蛋白激酶（SAPK）/c-Jun氨基末端激酶（JNK）是丝裂原活化蛋白激酶（MAPK）超家族的成员之一，在多种细胞过程中起关键作用。众所周知，SAPK/JNK的激活受上游丝裂原活化蛋白激酶激酶SEK1/MKK4的控制。为了深入了解SEK1在胚胎发育和成年期的作用，我们通过原位杂交和免疫组织化学研究，检测了小鼠中sek1表达的时空模式。在胚胎发生过程中观察到sek1表达的动态变化。在发育早期，在大多数中枢神经系统、肝脏和胸腺中检测到强烈的sek1表达。虽然神经系统中sek1的表达随时间增加，但随着胚胎发育的进行，胎儿肝脏和胸腺中的表达逐渐减少。中枢神经系统中sek1的高表达在出生后发育过程中持续存在，并在成年大脑中保持稳定水平。这些观察结果为SEK1在发育过程中的重要作用，例如在肝脏发生和/或神经发生中，提供了解剖学基础。虽然SEK在成年大脑中广泛表达，但在大脑皮层的第2层和第6层、小脑的浦肯野细胞以及下丘脑核中观察到sek1的更强表达。sek1的最强表达出现在海马体的CA3区域，在红藻氨酸处理的动物模型中，该区域极易受到兴奋毒性诱导的细胞凋亡的影响。有趣的是，根据成年小鼠大脑的区域不同，SEK1不仅定位于细胞质中，还定位于神经元的树突和/或细胞核中。综上所述，这些结果表明SEK1在胚胎发生和成年大脑中具有多种作用。
