Marcinkiewicz M, Nagao T, Day R, Seidah N G, Chrétien M, Avoli M
J. A. DeSève Laboratory of Molecular Neuroendocrinology, University ofMontreal, Quebec, Canada.
Neuroscience. 1997 Jan;76(2):425-39. doi: 10.1016/s0306-4522(96)00318-1.
Several prohormone convertases that are involved in the posttranslational processing of precursor proteins, including neuropetides, hormones and neurotrophic factors, are produced in the central nervous system. These include enzymes named furin, PC1, PC2, PC5 and PACE4. To understand better the potential role played by prohormone convertases in the central nervous system we studied the expression of their messenger RNAs in the hippocampus of rats with pilocarpine-induced seizures. Moreover, we compared their expression patterns with those of neurotrophins such as nerve growth factor and brain-derived neurotrophic factor, which are up-regulated in the hippocampus during seizures. Pilocarpine (380 mg/kg, i.p.) induced seizure activity that appeared within the first hour and persisted for approximately 8 h. In situ hybridization showed transient increases in messenger RNA for nerve growth factor and brain-derived neurotrophic factor that peaked at 120 min in the hippocampus. Among the convertases studied, only PC1 messenger RNA displayed up-regulation, with temporal and topographic features comparable to those of nerve growth factor and brain-derived neurotrophic factor messenger RNA. The expression of furin, PC2 and PC5 messenger RNA changed little, while PACE4 was not expressed at all, both before and after pilocarpine administration. The highest increase in PC1 messenger RNA expression was found in granule cells of the dentate gyrus and, to a lesser extent, in the pyramidal layer of CA1 and CA3 subfields. Thus, in the rat hippocampus, the epileptiform activity induced by pilocarpine mediates a co-ordinated expression of messenger RNAs for PC1, nerve growth factor and brain-derived neurotrophic factor. Our findings suggest the involvement of PC1 in the processing of precursor proteins during seizure activity.
几种参与前体蛋白（包括神经肽、激素和神经营养因子）翻译后加工的激素原转化酶在中枢神经系统中产生。这些酶包括弗林蛋白酶、PC1、PC2、PC5和PACE4。为了更好地理解激素原转化酶在中枢神经系统中所起的潜在作用，我们研究了它们的信使核糖核酸在毛果芸香碱诱导癫痫发作的大鼠海马体中的表达。此外，我们将它们的表达模式与神经营养因子（如神经生长因子和脑源性神经营养因子）的表达模式进行了比较，这些神经营养因子在癫痫发作时海马体中表达上调。毛果芸香碱（380毫克/千克，腹腔注射）诱导的癫痫活动在第一小时内出现，并持续约8小时。原位杂交显示神经生长因子和脑源性神经营养因子的信使核糖核酸短暂增加，在海马体中于120分钟时达到峰值。在所研究的转化酶中，只有PC1信使核糖核酸显示上调，其时间和拓扑特征与神经生长因子和脑源性神经营养因子信使核糖核酸的特征相当。弗林蛋白酶、PC2和PC5信使核糖核酸的表达变化不大，而PACE4在毛果芸香碱给药前后均未表达。PC1信使核糖核酸表达增加最多的是齿状回颗粒细胞，在较小程度上是CA1和CA3亚区的锥体细胞层。因此，在大鼠海马体中，毛果芸香碱诱导的癫痫样活动介导了PC1、神经生长因子和脑源性神经营养因子信使核糖核酸的协同表达。我们的研究结果表明PC1参与了癫痫发作活动期间前体蛋白的加工过程。
