Herdegen T, Gass P, Brecht S, Neiss W F, Schmid W
II. Institute of Physiology, University of Heidelberg, FRG.
Brain Res Mol Brain Res. 1994 Oct;26(1-2):259-70. doi: 10.1016/0169-328x(94)90098-1.
The present study has investigated whether nerve fiber transection alters the phosphorylation of serine at position 133 (Ser133) of the transcription factor CREB (phosphoCREB). Activation of CREB by phosphorylation has a major function in the control of gene transcription. PhosphoCREB was visualized by antisera that specifically react with an epitope comprising the phosphorylated Ser133 of CREB as well as of CREM and ATF1 proteins. In untreated rats, nuclear immunoreactivity (IR) of phosphoCREB was consistently visible, e.g. in the cortex, thalamic and hypothalamic compartments and central termination areas of primary somatosensory afferents. Transection of peripheral (sciatic nerve), cranial (hypoglossal and facial nerve) and central (medial forebrain bundle and mammillo-thalamic tract) nerve fibers did not increase phosphoCREB-IR in the axotomized neurons between 5 min and 30 days post-axotomy. In contrast, phosphoCREB-IR appeared after 24 h in glial cells adjacent to the axotomized motoneurons and persisted up to 4 weeks. This increase in glial phosphoCREB-IR was paralleled by enhanced expression of the CREB protein itself. Between 20 min and 24 h following sciatic nerve transection, the number of phosphoCREB labeled nuclei also increased in neurons of the ipsilateral superficial dorsal horn of lumbar L3-L5 spinal cord segments. These data suggest that phosphorylation of Ser133 in CREB/CREM/ATF1 proteins is not involved in the transcriptional control of early-response genes such as c-jun in axotomized neurons following nerve transection. This is in contrast to the reported phosphorylation of CREB and its trans-acting effects on immediate-early genes such as c-fos after transynaptic neuronal excitation.
本研究调查了神经纤维横断是否会改变转录因子CREB第133位丝氨酸（Ser133）的磷酸化（磷酸化CREB）。磷酸化激活CREB在基因转录控制中起主要作用。磷酸化CREB通过与包含CREB以及CREM和ATF1蛋白磷酸化Ser133的表位特异性反应的抗血清来可视化。在未处理的大鼠中，磷酸化CREB的核免疫反应性（IR）始终可见，例如在皮质、丘脑和下丘脑区域以及初级体感传入神经的中枢终末区域。外周（坐骨神经）、颅神经（舌下神经和面神经）和中枢（内侧前脑束和乳头体 - 丘脑束）神经纤维横断在轴突横断后5分钟至30天内，并未增加轴突切断神经元中的磷酸化CREB - IR。相反，磷酸化CREB - IR在与轴突切断的运动神经元相邻的神经胶质细胞中在24小时后出现，并持续长达4周。神经胶质细胞中磷酸化CREB - IR的这种增加与CREB蛋白本身表达的增强相平行。在坐骨神经横断后20分钟至24小时之间，腰段L3 - L5脊髓节段同侧浅表背角神经元中磷酸化CREB标记的细胞核数量也增加。这些数据表明，在神经横断后，CREB/CREM/ATF1蛋白中Ser133的磷酸化不参与轴突切断神经元中早期反应基因（如c - jun）的转录控制。这与报道的CREB磷酸化及其对经突触神经元兴奋后立即早期基因（如c - fos）的反式作用形成对比。
