Neuropeptides, Growth Factors, and Cytokines: A Cohort of Informational Molecules Whose Expression Is Up-Regulated by the Stress-Associated Slow Transmitter PACAP in Chromaffin Cells
Neuropeptides, Growth Factors, and Cytokines: A Cohort of Informational Molecules Whose Expression Is Up-Regulated by the Stress-Associated Slow Transmitter PACAP in Chromaffin Cells
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DOI：
10.1007/s10571-010-9620-y
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发表时间：
2010-11-01
影响因子：
4
通讯作者：
Eiden, Lee E.
中科院分区：
文献类型：
--
作者：
Ait-Ali, Djida;Samal, Babru;Eiden, Lee E.
垂体腺苷环化酶激活多肽(PACAP)是肾上腺髓质突触与乙酰胆碱的共递质，在基因转录水平上介导持续的激素分泌和应激反应中细胞可塑性的调节。在这里，我们将我们对PACAP调控的神经内分泌细胞特异性基因的研究从PC12细胞扩展到PC12细胞，表达体内嗜铬细胞上发现的PAC1hop受体的生理水平。与PC12细胞相比，PACAP在这些PC12_bPAC1hop细胞中诱导了额外的一组基因，富含信息分子，包括细胞因子、神经肽和生长因子。利用两个新开发的表达牛转录本的微阵列平台，我们进一步检测了PACAP在牛嗜铬细胞中的诱导基因，在暴露期间(6h)对应于体内长期的代谢或心理应激，在此期间PACAP从内脏神经释放到嗜铬细胞。与PC12_bPAC1hop细胞一样，PACAP在牛嗜铬细胞中诱导了一组编码分泌蛋白的基因，通过独创性路径分析对其进行细胞定位，这些基因高度富含信息分子(作用于细胞外受体的分泌蛋白)。这些包括细胞因子、生长因子和激素，以及转换酶，或调节转换酶功能的蛋白酶抑制剂。鉴定了几个以前在嗜铬细胞中未被PACAP调控的神经肽前激素转录本，如促甲状腺激素释放激素和速激肽前体1。对这组信息分子编码转录本的鉴定表明，PACAP作为肾上腺髓质中特定的压力转导的共同递质，具有更广泛、更完整的作用。
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a co-transmitter with acetylcholine at the adrenomedullary synapse, mediating sustained hormone secretion and regulation of cellular plasticity in response to stress at the level of gene transcription. Here we have extended our investigation of PACAP-regulated neuroendocrine cell-specific genes from PC12 cells to PC12 cells expressing physiological levels of the PAC1hop receptor found on chromaffin cells in vivo. PACAP induces in these PC12_bPAC1hop cells an additional cohort of genes, compared to PC12 cells, enriched in informational molecules including cytokines, neuropeptides, and growth factors. Using two newly developed microarray platforms for expressed bovine transcripts, we further examined PACAP-induced genes in bovine chromaffin cells during a period of exposure (6 h) corresponding to a period of prolonged metabolic or psychogenic stress in vivo during which PACAP is released from the splanchnic nerve onto chromaffin cells. As in PC12_bPAC1hop cells, PACAP induced in bovine chromaffin cells a cohort of genes encoding secretory proteins, identified by tiling for cellular localization using Ingenuity Pathway Analysis, which were highly enriched in informational molecules (secreted proteins acting at extracellular receptors). These included cytokines, growth factors and hormones, as well as converting enzymes, or protease inhibitors modulating converting enzyme function. Several neuropeptide prohormone transcripts not previously shown to be PACAP-regulated in chromaffin cells, such as thyrotropin-releasing hormone, and tachykinin precursor 1, were identified. Identification of this cohort of informational molecule-encoding transcripts suggests a wider, more integrative role for PACAP as a co-transmitter specific to stress transduction in the adrenal medulla.