Catestatin regulates vesicular quanta through modulation of cholinergic and peptidergic (PACAPergic) stimulation in PC12 cells.
Catestatin regulates vesicular quanta through modulation of cholinergic and peptidergic (PACAPergic) stimulation in PC12 cells.
复制标题
Catestatin 通过调节 PC12 细胞中的胆碱能和肽能 (PACAPergic) 刺激来调节囊泡量子。
DOI：
10.1007/s00441-018-2956-1
复制
发表时间：
2019
影响因子：
3.6
通讯作者：
Corti,A
中科院分区：
文献类型：
--
作者：
Sahu,BhavaniShankar;Mahata,Sumana;Bandyopadhyay,Keya;Mahata,Manjula;Avolio,Ennio;Pasqua,Teresa;Sahu,Chinmayi;Bandyopadhyay,GautamK;Bartolomucci,Alessandro;Webster,NicholasJG;VanDenBogaart,Geert;Fischer-Colbrie,Reiner;Corti,A
我们以前已经表明，嗜铬粒蛋白A（CgA）衍生的肽catestatin（CST：hCgA 352 -372）抑制尼古丁诱导的肾上腺髓质和嗜铬细胞分泌的儿茶酚胺。在本研究中，我们试图确定CST是否调节致密核心（DC）囊泡（DCV）量子（儿茶酚胺和嗜铬粒蛋白/分泌粒蛋白）在急性（0.5小时治疗）或慢性（24小时治疗）胆碱能（尼古丁）或肽能（PACAP，垂体腺苷酸环化酶激活多肽）刺激的PC 12细胞。在急性实验中，我们发现尼古丁（60 μM）和PACAP（0.1 μM）均降低细胞内去甲肾上腺素（NE）含量并增加3 H-NE分泌，与CST（2 μM）共同处理可显著抑制这两种作用。在慢性实验中，我们发现尼古丁和PACAP都降低了DCV和DC直径，并且CST也阻止了这种作用。尼古丁或CST单独增加CgA蛋白的表达，并共同引起CgA蛋白的额外增加，这意味着尼古丁和CST利用单独的信号通路来激活CgA表达。相反，PACAP增加CgB和SgII蛋白的表达，CST进一步增强。CST增强了酪氨酸羟化酶（TH）的表达，但没有增加细胞内NE水平，可能是由于其无法通过丝氨酸磷酸化引起TH的翻译后激活。CST与尼古丁或PACAP的共处理增加了量子尺寸，这可能是由于CST增加了CgA、CgB和SgII的合成。我们的结论是，CST调节DCV量子急性抑制儿茶酚胺分泌和慢性烟碱刺激后CgA的表达和CgB和SgII后PACA Pergic刺激。
We have previously shown that the chromogranin A (CgA)-derived peptide catestatin (CST: hCgA352–372) inhibits nicotine-induced secretion of catecholamines from the adrenal medulla and chromaffin cells. In the present study, we seek to determine whether CST regulates dense core (DC) vesicle (DCV) quanta (catecholamine and chromogranin/secretogranin proteins) during acute (0.5-h treatment) or chronic (24-h treatment) cholinergic (nicotine) or peptidergic (PACAP, pituitary adenylyl cyclase activating polypeptide) stimulation of PC12 cells. In acute experiments, we found that both nicotine (60 μM) and PACAP (0.1 μM) decreased intracellular norepinephrine (NE) content and increased3H‐NE secretion, with both effects markedly inhibited by co-treatment with CST (2 μM). In chronic experiments, we found that nicotine and PACAP both reduced DCV and DC diameters and that this effect was likewise prevented by CST. Nicotine or CST alone increased expression of CgA protein and together elicited an additional increase in CgA protein, implying that nicotine and CST utilize separate signaling pathways to activate CgA expression. In contrast, PACAP increased expression of CgB and SgII proteins, with a further potentiation by CST. CST augmented the expression of tyrosine hydroxylase (TH) but did not increase intracellular NE levels, presumably due to its inability to cause post-translational activation of TH through serine phosphorylation. Co-treatment of CST with nicotine or PACAP increased quantal size, plausibly due to increased synthesis of CgA, CgB and SgII by CST. We conclude that CST regulates DCV quanta by acutely inhibiting catecholamine secretion and chronically increasing expression of CgA after nicotinic stimulation and CgB and SgII after PACAPergic stimulation.