Villalba M, Bockaert J, Journot L
Centre National de la Recherche Scientifique (CNRS), Unité Propre de Recherche 9023, Centre CNRS-Institut National de la Santé et de la Recherche Médicale de Pharmacologie-Endocrinologie, F-34094 Montpellier Cedex 05, France.
J Neurosci. 1997 Jan 1;17(1):83-90. doi: 10.1523/JNEUROSCI.17-01-00083.1997.
Pituitary adenylate cyclase-activating polypeptides (PACAP-27 and PACAP-38) are neuropeptides of the vasoactive intestinal polypeptide (VIP)/secretin/glucagon family. PACAP receptors are expressed in different brain regions, including cerebellum. We used primary culture of rat cerebellar granule neurons to study the effect of PACAP-38 on apoptosis induced by potassium deprivation. We demonstrated that PACAP-38 increased survival of cerebellar neurons in a dose-dependent manner by decreasing the extent of apoptosis estimated by DNA fragmentation. PACAP-38 induced activation of the extracellular signal-regulated kinase (ERK)-type of mitogen-activated protein (MAP) kinase through a cAMP-dependent pathway. PD98059, an inhibitor of MEK (MAP kinase kinase), completely abolished the antiapoptotic effect of PACAP-38, suggesting that MAP kinase pathway activation is necessary for PACAP-38 action.
垂体腺苷酸环化酶激活多肽(PACAP - 27和PACAP - 38)是血管活性肠多肽(VIP)/促胰液素/胰高血糖素家族的神经肽。PACAP受体在包括小脑在内的不同脑区表达。我们使用大鼠小脑颗粒神经元原代培养物来研究PACAP - 38对钾缺乏诱导的细胞凋亡的影响。我们证明,PACAP - 38通过降低DNA片段化估计的凋亡程度,以剂量依赖性方式增加小脑神经元的存活率。PACAP - 38通过cAMP依赖性途径诱导细胞外信号调节激酶(ERK)型丝裂原活化蛋白(MAP)激酶的激活。MEK(MAP激酶激酶)抑制剂PD98059完全消除了PACAP - 38的抗凋亡作用,表明MAP激酶途径激活对于PACAP - 38的作用是必要的。