垂体腺苷酸环化酶激活多肽（PACAP - 38）通过激活丝裂原活化蛋白激酶（MAP激酶）途径保护小脑颗粒神经元免于凋亡。
Pituitary adenylate cyclase-activating polypeptide (PACAP-38) protects cerebellar granule neurons from apoptosis by activating the mitogen-activated protein kinase (MAP kinase) pathway.
作者信息
Villalba M, Bockaert J, Journot L
机构信息
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.
出版信息
J Neurosci. 1997 Jan 1;17(1):83-90. doi: 10.1523/JNEUROSCI.17-01-00083.1997.
Abstract
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.
摘要
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。
相似文献
1
Pituitary adenylate cyclase-activating polypeptide (PACAP-38) protects cerebellar granule neurons from apoptosis by activating the mitogen-activated protein kinase (MAP kinase) pathway.垂体腺苷酸环化酶激活多肽（PACAP - 38）通过激活丝裂原活化蛋白激酶（MAP激酶）途径保护小脑颗粒神经元免于凋亡。
J Neurosci. 1997 Jan 1;17(1):83-90. doi: 10.1523/JNEUROSCI.17-01-00083.1997.
2
PACAP-38 protects cerebellar granule cells from apoptosis.垂体腺苷酸环化酶激活肽-38可保护小脑颗粒细胞免于凋亡。
Ann N Y Acad Sci. 1998 Dec 11;865:100-10. doi: 10.1111/j.1749-6632.1998.tb11168.x.
3
Pituitary adenylate cyclase activating polypeptide prevents apoptosis in cultured cerebellar granule neurons.垂体腺苷酸环化酶激活多肽可防止培养的小脑颗粒神经元发生凋亡。
Mol Pharmacol. 1996 Jul;50(1):60-6.
4
Pituitary adenylate cyclase-activating polypeptide prevents C2-ceramide-induced apoptosis of cerebellar granule cells.垂体腺苷酸环化酶激活多肽可防止C2-神经酰胺诱导的小脑颗粒细胞凋亡。
J Neurosci Res. 2003 May 1;72(3):303-16. doi: 10.1002/jnr.10530.
5
The neuroprotective effect of pituitary adenylate cyclase-activating polypeptide on cerebellar granule cells is mediated through inhibition of the CED3-related cysteine protease caspase-3/CPP32.垂体腺苷酸环化酶激活多肽对小脑颗粒细胞的神经保护作用是通过抑制与CED3相关的半胱氨酸蛋白酶caspase-3/CPP32介导的。
Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13390-5. doi: 10.1073/pnas.97.24.13390.
6
Pituitary adenylate cyclase-activating polypeptide stimulates both c-fos gene expression and cell survival in rat cerebellar granule neurons through activation of the protein kinase A pathway.垂体腺苷酸环化酶激活多肽通过蛋白激酶A途径的激活，刺激大鼠小脑颗粒神经元中的c-fos基因表达和细胞存活。
Neuroscience. 1998 Jun;84(3):801-12. doi: 10.1016/s0306-4522(97)00545-9.
7
Facilitatory effects of pituitary adenylate cyclase activating polypeptide (PACAP) on neurons in the magnocellular portion of the rat hypothalamic paraventricular nucleus (PVN) in vitro.垂体腺苷酸环化酶激活多肽（PACAP）对大鼠下丘脑室旁核（PVN）大细胞部神经元的体外促进作用。
J Neuroendocrinol. 1996 Feb;8(2):137-43. doi: 10.1111/j.1365-2826.1996.tb00834.x.
8
Characterization of vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptors in human benign hyperplastic prostate.人良性增生前列腺中血管活性肠肽/垂体腺苷酸环化酶激活肽受体的特征分析
Endocrinology. 1996 Jul;137(7):2815-22. doi: 10.1210/endo.137.7.8770902.
9
Evidence for roles of vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) receptors in modulating the responses of rat dorsal horn neurons to sensory inputs.血管活性肠肽（VIP）和垂体腺苷酸环化酶激活肽（PACAP）受体在调节大鼠背角神经元对感觉输入反应中的作用证据。
Neuropeptides. 1997 Apr;31(2):175-85. doi: 10.1016/s0143-4179(97)90087-1.
10
Pituitary adenylyl cyclase-activating peptide stimulates extracellular signal-regulated kinase 1 or 2 (ERK1/2) activity in a Ras-independent, mitogen-activated protein Kinase/ERK kinase 1 or 2-dependent manner in PC12 cells.垂体腺苷酸环化酶激活肽以一种不依赖Ras、依赖丝裂原活化蛋白激酶/细胞外信号调节激酶1或2（MEK1/2）的方式刺激PC12细胞中的细胞外信号调节激酶1或2（ERK1/2）活性。
J Biol Chem. 1997 Aug 8;272(32):19666-71. doi: 10.1074/jbc.272.32.19666.
引用本文的文献
1
Somatostatin receptor 2 targeting peptide modifications for peptide-drug conjugate treatment of small cell lung cancer.用于肽-药物偶联物治疗小细胞肺癌的靶向生长抑素受体2的肽修饰
Acta Pharmacol Sin. 2025 Jun 18. doi: 10.1038/s41401-025-01584-w.
2
Cerebro-Cerebellar Networks in Migraine Symptoms and Headache.偏头痛症状与头痛中的脑-小脑网络
Front Pain Res (Lausanne). 2022 Jul 13;3:940923. doi: 10.3389/fpain.2022.940923. eCollection 2022.
3
Effects of Pituitary Adenylate Cyclase Activating Polypeptide on Cell Death.垂体腺苷酸环化酶激活肽对细胞死亡的影响。
Int J Mol Sci. 2022 Apr 29;23(9):4953. doi: 10.3390/ijms23094953.
4
Adaptive Changes in the Central Control of Energy Homeostasis Occur in Response to Variations in Energy Status.能量平衡的中枢控制会发生适应性变化以响应能量状态的变化。
Int J Mol Sci. 2021 Mar 8;22(5):2728. doi: 10.3390/ijms22052728.
5
Pituitary Adenylate Cyclase-Activating Polypeptide: A Promising Neuroprotective Peptide in Stroke.垂体腺苷酸环化酶激活多肽：一种在中风中颇具前景的神经保护肽。
Aging Dis. 2020 Dec 1;11(6):1496-1512. doi: 10.14336/AD.2020.0626. eCollection 2020 Dec.
6
Vasoactive Intestinal Peptide induces glucose and neutral amino acid uptake through mTOR signalling in human cytotrophoblast cells.血管活性肠肽通过人细胞滋养层细胞中的 mTOR 信号诱导葡萄糖和中性氨基酸摄取。
Sci Rep. 2019 Nov 20;9(1):17152. doi: 10.1038/s41598-019-53676-3.
7
Essential Oil and Linalool Counteract Social Aversion Induced by Social Defeat.精油和芳樟醇可对抗社交挫败引起的社交回避。
Molecules. 2018 Oct 19;23(10):2694. doi: 10.3390/molecules23102694.
8
AMPK Activation of PGC-1α/NRF-1-Dependent SELENOT Gene Transcription Promotes PACAP-Induced Neuroendocrine Cell Differentiation Through Tolerance to Oxidative Stress.AMPK 激活 PGC-1α/NRF-1 依赖性 SELENOT 基因转录通过耐受氧化应激促进 PACAP 诱导的神经内分泌细胞分化。
Mol Neurobiol. 2019 Jun;56(6):4086-4101. doi: 10.1007/s12035-018-1352-x. Epub 2018 Sep 28.
9
Nicotine is neuroprotective to neonatal neurons of sympathetic ganglion in rat.尼古丁对新生大鼠交感神经节神经元具有神经保护作用。
Auton Neurosci. 2019 Jan;216:25-32. doi: 10.1016/j.autneu.2018.08.004. Epub 2018 Sep 4.
10
Danggui Buxue Tang, a simple Chinese formula containing Astragali Radix and Angelicae Sinensis Radix, stimulates the expressions of neurotrophic factors in cultured SH-SY5Y cells.当归补血汤是一种由黄芪和当归组成的简单中药方剂，可刺激培养的SH-SY5Y细胞中神经营养因子的表达。
Chin Med. 2017 Aug 22;12:24. doi: 10.1186/s13020-017-0144-y. eCollection 2017.
本文引用的文献
1
Nerve growth factor withdrawal induces the apoptotic death of developing septal cholinergic neurons in vitro: protection by cyclic AMP analogue and high potassium.
Neuroscience. 1996 Jan;70(2):329-39. doi: 10.1016/0306-4522(95)00365-7.
2
Tissue-specific and developmental expression of pituitary adenylate cyclase-activating polypeptide (PACAP) receptors in rat brain.大鼠脑中垂体腺苷酸环化酶激活多肽（PACAP）受体的组织特异性和发育表达。
Eur J Neurosci. 1996 Feb;8(2):310-8. doi: 10.1111/j.1460-9568.1996.tb01215.x.
3
Activation of p44 and p42 MAP kinases is not essential for the survival of rat sympathetic neurons.
Eur J Neurosci. 1995 Oct 1;7(10):2159-69. doi: 10.1111/j.1460-9568.1995.tb00637.x.
4
In situ labeling of granule cells for apoptosis-associated DNA fragmentation reveals different mechanisms of cell loss in developing cerebellum.对颗粒细胞凋亡相关DNA片段进行原位标记，揭示了发育中小脑细胞丢失的不同机制。
Neuron. 1993 Oct;11(4):621-32. doi: 10.1016/0896-6273(93)90074-2.
5
Differential signal transduction by five splice variants of the PACAP receptor.垂体腺苷酸环化酶激活肽（PACAP）受体的五种剪接变体的差异信号转导
Nature. 1993 Sep 9;365(6442):170-5. doi: 10.1038/365170a0.
6
Molecular cloning and tissue distribution of a receptor for pituitary adenylate cyclase-activating polypeptide.垂体腺苷酸环化酶激活多肽受体的分子克隆与组织分布
Neuron. 1993 Aug;11(2):333-42. doi: 10.1016/0896-6273(93)90188-w.
7
Ca(2+)-dependent stimulatory effect of pituitary adenylate cyclase-activating polypeptide on catecholamine secretion from cultured porcine adrenal medullary chromaffin cells.垂体腺苷酸环化酶激活多肽对培养的猪肾上腺髓质嗜铬细胞儿茶酚胺分泌的钙离子依赖性刺激作用。
Endocrinology. 1993 Apr;132(4):1757-65. doi: 10.1210/endo.132.4.8384995.
8
Differentiation of PC12 cells in response to a cAMP analogue is accompanied by sustained activation of mitogen-activated protein kinase. Comparison with the effects of insulin, growth factors and phorbol esters.PC12细胞对环磷酸腺苷类似物的分化反应伴随着丝裂原活化蛋白激酶的持续激活。与胰岛素、生长因子和佛波酯作用的比较。
FEBS Lett. 1994 Jan 31;338(2):212-6. doi: 10.1016/0014-5793(94)80367-6.
9
Induction of apoptosis in cerebellar granule neurons by low potassium: inhibition of death by insulin-like growth factor I and cAMP.低钾诱导小脑颗粒神经元凋亡：胰岛素样生长因子I和环磷酸腺苷对细胞死亡的抑制作用
Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10989-93. doi: 10.1073/pnas.90.23.10989.
10
The VIP2 receptor: molecular characterisation of a cDNA encoding a novel receptor for vasoactive intestinal peptide.血管活性肠肽2型受体：编码血管活性肠肽新型受体的cDNA的分子特征
FEBS Lett. 1993 Nov 8;334(1):3-8. doi: 10.1016/0014-5793(93)81668-p.
Zotero 插件