RAPID INCREASES IN PEPTIDE PROCESSING ENZYME EXPRESSION IN HIPPOCAMPAL-NEURONS
RAPID INCREASES IN PEPTIDE PROCESSING ENZYME EXPRESSION IN HIPPOCAMPAL-NEURONS
复制标题
DOI：
10.1111/j.1471-4159.1993.tb13624.x
复制
发表时间：
1993-10-01
影响因子：
4.7
通讯作者：
EIPPER, BA
中科院分区：
文献类型：
--
作者：
BHAT, RV;TAUSK, FA;EIPPER, BA
最近的研究表明，惊厥活动导致大鼠海马区特定区域神经肽表达显著增加。在这项研究中，我们研究了电休克处理(ECT)对三种翻译后加工酶表达的影响，这些酶参与了许多生物活性多肽的合成。多肽甘氨酸α-酰胺化单加氧酶(PAM)将多肽甘氨酸底物转化为α-酰胺化产物，前激素转化酶1和2执行许多前激素的组织特异性内蛋白分解。单次ECT后，原位杂交显示海马齿状颗粒细胞PAM mRNA表达水平迅速升高，1~4h达到高峰，24 h内恢复到接近基线水平，Northern印迹分析证实原位杂交证实了PAM mRNA表达的变化。重复电刺激后PAM基因表达也有类似的快速变化，提示慢性电刺激不影响海马区PAM基因表达的调节。免疫组织化学染色显示，单次电刺激后4h和8h，齿状回分子层PAM蛋白表达增加。基于原位杂交，在单次ECT后，齿状颗粒细胞中前激素转换酶1和2的mRNA水平也增加。前激素转换酶2mRNA水平对ECT的反应较慢，直到ECT后8h才达到最高水平。海马齿状颗粒细胞对电刺激的反应为研究多肽加工酶的快速、协调调节提供了一个模型系统。
Recent studies have demonstrated that seizure activity causes a dramatic increase in neuropeptide expression in specific regions of the rat hippocampus. In this study we investigated the effect of electroconvulsive treatment (ECT) on the expression of three posttranslational processing enzymes involved in the production of many bioactive peptides from their inactive precursors. Peptidylglycine alpha-amidating monooxygenase (PAM) converts peptidylglycine substrates into alpha-amidated products and prohormone convertases 1 and 2 perform the tissue-specific endoproteolytic cleavage of many prohormones. After a single ECT, in situ hybridization demonstrated a rapid increase in the level of PAM mRNA in the dentate granule cells of the hippocampus, reaching peak levels between 1 and 4 h and then returning to near baseline levels within 24 h. Northern blot analysis confirmed the changes in PAM mRNA expression seen by using in situ hybridization. Similar rapid changes in PAM mRNA expression were seen after repeated ECT, suggesting that chronic ECT did not affect the regulation of PAM expression in the hippocampus. Immunohistochemical staining demonstrated an increase in PAM protein in the molecular layer of the dentate gyrus at 4 and 8 h after a single ECT. Based on in situ hybridization, levels of mRNA for the prohormone convertases 1 and 2 were also increased in dentate granule cells after a single ECT. Prohormone convertase 2 mRNA levels exhibited a slower response to ECT, not reaching maximal levels until 8 h after ECT. The response of the dentate granule cells of the hippocampus to ECT provides a model system for studying the rapid, coordinate regulation of peptide-processing enzymes.